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+anno_start	anno_end	anno_text	entity_type	sentence	section
+0	9	Structure	evidence	Structure of the Response Regulator NsrR from Streptococcus agalactiae, Which Is Involved in Lantibiotic Resistance	TITLE
+17	35	Response Regulator	protein_type	Structure of the Response Regulator NsrR from Streptococcus agalactiae, Which Is Involved in Lantibiotic Resistance	TITLE
+36	40	NsrR	protein	Structure of the Response Regulator NsrR from Streptococcus agalactiae, Which Is Involved in Lantibiotic Resistance	TITLE
+46	70	Streptococcus agalactiae	species	Structure of the Response Regulator NsrR from Streptococcus agalactiae, Which Is Involved in Lantibiotic Resistance	TITLE
+93	104	Lantibiotic	chemical	Structure of the Response Regulator NsrR from Streptococcus agalactiae, Which Is Involved in Lantibiotic Resistance	TITLE
+0	12	Lantibiotics	chemical	Lantibiotics are antimicrobial peptides produced by Gram-positive bacteria.	ABSTRACT
+17	39	antimicrobial peptides	chemical	Lantibiotics are antimicrobial peptides produced by Gram-positive bacteria.	ABSTRACT
+52	74	Gram-positive bacteria	taxonomy_domain	Lantibiotics are antimicrobial peptides produced by Gram-positive bacteria.	ABSTRACT
+47	52	human	species	Interestingly, several clinically relevant and human pathogenic strains are inherently resistant towards lantibiotics.	ABSTRACT
+105	117	lantibiotics	chemical	Interestingly, several clinically relevant and human pathogenic strains are inherently resistant towards lantibiotics.	ABSTRACT
+44	55	lantibiotic	chemical	The expression of the genes responsible for lantibiotic resistance is regulated by a specific two-component system consisting of a histidine kinase and a response regulator.	ABSTRACT
+94	114	two-component system	complex_assembly	The expression of the genes responsible for lantibiotic resistance is regulated by a specific two-component system consisting of a histidine kinase and a response regulator.	ABSTRACT
+131	147	histidine kinase	protein_type	The expression of the genes responsible for lantibiotic resistance is regulated by a specific two-component system consisting of a histidine kinase and a response regulator.	ABSTRACT
+154	172	response regulator	protein_type	The expression of the genes responsible for lantibiotic resistance is regulated by a specific two-component system consisting of a histidine kinase and a response regulator.	ABSTRACT
+22	40	response regulator	protein_type	Here, we focused on a response regulator involved in lantibiotic resistance, NsrR from Streptococcus agalactiae, and determined the crystal structures of its N-terminal receiver domain and C-terminal DNA-binding effector domain.	ABSTRACT
+53	64	lantibiotic	chemical	Here, we focused on a response regulator involved in lantibiotic resistance, NsrR from Streptococcus agalactiae, and determined the crystal structures of its N-terminal receiver domain and C-terminal DNA-binding effector domain.	ABSTRACT
+77	81	NsrR	protein	Here, we focused on a response regulator involved in lantibiotic resistance, NsrR from Streptococcus agalactiae, and determined the crystal structures of its N-terminal receiver domain and C-terminal DNA-binding effector domain.	ABSTRACT
+87	111	Streptococcus agalactiae	species	Here, we focused on a response regulator involved in lantibiotic resistance, NsrR from Streptococcus agalactiae, and determined the crystal structures of its N-terminal receiver domain and C-terminal DNA-binding effector domain.	ABSTRACT
+132	150	crystal structures	evidence	Here, we focused on a response regulator involved in lantibiotic resistance, NsrR from Streptococcus agalactiae, and determined the crystal structures of its N-terminal receiver domain and C-terminal DNA-binding effector domain.	ABSTRACT
+169	184	receiver domain	structure_element	Here, we focused on a response regulator involved in lantibiotic resistance, NsrR from Streptococcus agalactiae, and determined the crystal structures of its N-terminal receiver domain and C-terminal DNA-binding effector domain.	ABSTRACT
+200	227	DNA-binding effector domain	structure_element	Here, we focused on a response regulator involved in lantibiotic resistance, NsrR from Streptococcus agalactiae, and determined the crystal structures of its N-terminal receiver domain and C-terminal DNA-binding effector domain.	ABSTRACT
+4	21	C-terminal domain	structure_element	The C-terminal domain exhibits a fold that classifies NsrR as a member of the OmpR/PhoB subfamily of regulators.	ABSTRACT
+54	58	NsrR	protein	The C-terminal domain exhibits a fold that classifies NsrR as a member of the OmpR/PhoB subfamily of regulators.	ABSTRACT
+78	97	OmpR/PhoB subfamily	protein_type	The C-terminal domain exhibits a fold that classifies NsrR as a member of the OmpR/PhoB subfamily of regulators.	ABSTRACT
+24	39	phosphorylation	ptm	Amino acids involved in phosphorylation, dimerization, and DNA-binding were identified and demonstrated to be conserved in lantibiotic resistance regulators.	ABSTRACT
+59	62	DNA	chemical	Amino acids involved in phosphorylation, dimerization, and DNA-binding were identified and demonstrated to be conserved in lantibiotic resistance regulators.	ABSTRACT
+110	119	conserved	protein_state	Amino acids involved in phosphorylation, dimerization, and DNA-binding were identified and demonstrated to be conserved in lantibiotic resistance regulators.	ABSTRACT
+123	156	lantibiotic resistance regulators	protein_type	Amino acids involved in phosphorylation, dimerization, and DNA-binding were identified and demonstrated to be conserved in lantibiotic resistance regulators.	ABSTRACT
+24	35	full-length	protein_state	Finally, a model of the full-length NsrR in the active and inactive state provides insights into protein dimerization and DNA-binding.	ABSTRACT
+36	40	NsrR	protein	Finally, a model of the full-length NsrR in the active and inactive state provides insights into protein dimerization and DNA-binding.	ABSTRACT
+48	54	active	protein_state	Finally, a model of the full-length NsrR in the active and inactive state provides insights into protein dimerization and DNA-binding.	ABSTRACT
+59	67	inactive	protein_state	Finally, a model of the full-length NsrR in the active and inactive state provides insights into protein dimerization and DNA-binding.	ABSTRACT
+122	125	DNA	chemical	Finally, a model of the full-length NsrR in the active and inactive state provides insights into protein dimerization and DNA-binding.	ABSTRACT
+93	98	human	species	This has led to the search for novel antibiotics that can be used as pharmaceuticals against human pathogenic bacteria.	INTRO
+110	118	bacteria	taxonomy_domain	This has led to the search for novel antibiotics that can be used as pharmaceuticals against human pathogenic bacteria.	INTRO
+49	61	lantibiotics	chemical	One of the potential antibiotic alternatives are lantibiotics.	INTRO
+0	12	Lantibiotics	chemical	Lantibiotics are small antimicrobial peptides (30–50 amino acids in length), which are produced by several Gram-positive bacterial strains.	INTRO
+23	45	antimicrobial peptides	chemical	Lantibiotics are small antimicrobial peptides (30–50 amino acids in length), which are produced by several Gram-positive bacterial strains.	INTRO
+107	130	Gram-positive bacterial	taxonomy_domain	Lantibiotics are small antimicrobial peptides (30–50 amino acids in length), which are produced by several Gram-positive bacterial strains.	INTRO
+60	71	lanthionine	chemical	They are post-translationally modified and contain specific lanthionine/methyl-lanthionine rings, which are crucial for their high antimicrobial activity.	INTRO
+72	90	methyl-lanthionine	chemical	They are post-translationally modified and contain specific lanthionine/methyl-lanthionine rings, which are crucial for their high antimicrobial activity.	INTRO
+0	12	Lantibiotics	chemical	Lantibiotics are for example highly effective against various Gram-positive, human pathogenic bacteria including Streptococcus pneumoniae and several methicillin-resistant Staphylococcus aureus (MRSA) strains.	INTRO
+62	75	Gram-positive	taxonomy_domain	Lantibiotics are for example highly effective against various Gram-positive, human pathogenic bacteria including Streptococcus pneumoniae and several methicillin-resistant Staphylococcus aureus (MRSA) strains.	INTRO
+77	82	human	species	Lantibiotics are for example highly effective against various Gram-positive, human pathogenic bacteria including Streptococcus pneumoniae and several methicillin-resistant Staphylococcus aureus (MRSA) strains.	INTRO
+94	102	bacteria	taxonomy_domain	Lantibiotics are for example highly effective against various Gram-positive, human pathogenic bacteria including Streptococcus pneumoniae and several methicillin-resistant Staphylococcus aureus (MRSA) strains.	INTRO
+113	137	Streptococcus pneumoniae	species	Lantibiotics are for example highly effective against various Gram-positive, human pathogenic bacteria including Streptococcus pneumoniae and several methicillin-resistant Staphylococcus aureus (MRSA) strains.	INTRO
+150	193	methicillin-resistant Staphylococcus aureus	species	Lantibiotics are for example highly effective against various Gram-positive, human pathogenic bacteria including Streptococcus pneumoniae and several methicillin-resistant Staphylococcus aureus (MRSA) strains.	INTRO
+195	199	MRSA	species	Lantibiotics are for example highly effective against various Gram-positive, human pathogenic bacteria including Streptococcus pneumoniae and several methicillin-resistant Staphylococcus aureus (MRSA) strains.	INTRO
+20	32	lantibiotics	chemical	The high potency of lantibiotics for medical usage has already been noticed, and several lantibiotics are already included in clinical trials.	INTRO
+89	101	lantibiotics	chemical	The high potency of lantibiotics for medical usage has already been noticed, and several lantibiotics are already included in clinical trials.	INTRO
+0	5	Nisin	chemical	Nisin is the most prominent member of the lantibiotic family and is able to inhibit cell growth, penetrates the membranes of various Gram-positive bacteria, and is characterized by five specific (methyl-)lanthionine rings, which are crucial for stability and activity in the nanomolar range.	INTRO
+42	53	lantibiotic	chemical	Nisin is the most prominent member of the lantibiotic family and is able to inhibit cell growth, penetrates the membranes of various Gram-positive bacteria, and is characterized by five specific (methyl-)lanthionine rings, which are crucial for stability and activity in the nanomolar range.	INTRO
+133	155	Gram-positive bacteria	taxonomy_domain	Nisin is the most prominent member of the lantibiotic family and is able to inhibit cell growth, penetrates the membranes of various Gram-positive bacteria, and is characterized by five specific (methyl-)lanthionine rings, which are crucial for stability and activity in the nanomolar range.	INTRO
+10	21	lantibiotic	chemical	Thus, the lantibiotic producer strains have an inbuilt self-protection mechanism (immunity) to prevent cell death caused due to the action of its cognate lantibiotic.	INTRO
+154	165	lantibiotic	chemical	Thus, the lantibiotic producer strains have an inbuilt self-protection mechanism (immunity) to prevent cell death caused due to the action of its cognate lantibiotic.	INTRO
+35	66	membrane–associated lipoprotein	protein_type	This immunity system consists of a membrane–associated lipoprotein (usually referred to as LanI) and/or an ABC transporter (termed as LanFEG and comprising three subunits).	INTRO
+91	95	LanI	protein_type	This immunity system consists of a membrane–associated lipoprotein (usually referred to as LanI) and/or an ABC transporter (termed as LanFEG and comprising three subunits).	INTRO
+107	122	ABC transporter	protein_type	This immunity system consists of a membrane–associated lipoprotein (usually referred to as LanI) and/or an ABC transporter (termed as LanFEG and comprising three subunits).	INTRO
+134	140	LanFEG	protein_type	This immunity system consists of a membrane–associated lipoprotein (usually referred to as LanI) and/or an ABC transporter (termed as LanFEG and comprising three subunits).	INTRO
+14	26	lantibiotics	chemical	Although some lantibiotics such as Pep5, epicidin, epilancin, and lactocin S only require LanI for immunity, other lantibiotics with a dual mode of action involving pore formation and lipid II binding such as nisin, subtilin, epidermin, gallidermin, and lacticin 3147 require additionally the presence of LanFEG.	INTRO
+35	39	Pep5	chemical	Although some lantibiotics such as Pep5, epicidin, epilancin, and lactocin S only require LanI for immunity, other lantibiotics with a dual mode of action involving pore formation and lipid II binding such as nisin, subtilin, epidermin, gallidermin, and lacticin 3147 require additionally the presence of LanFEG.	INTRO
+41	49	epicidin	chemical	Although some lantibiotics such as Pep5, epicidin, epilancin, and lactocin S only require LanI for immunity, other lantibiotics with a dual mode of action involving pore formation and lipid II binding such as nisin, subtilin, epidermin, gallidermin, and lacticin 3147 require additionally the presence of LanFEG.	INTRO
+51	60	epilancin	chemical	Although some lantibiotics such as Pep5, epicidin, epilancin, and lactocin S only require LanI for immunity, other lantibiotics with a dual mode of action involving pore formation and lipid II binding such as nisin, subtilin, epidermin, gallidermin, and lacticin 3147 require additionally the presence of LanFEG.	INTRO
+66	76	lactocin S	chemical	Although some lantibiotics such as Pep5, epicidin, epilancin, and lactocin S only require LanI for immunity, other lantibiotics with a dual mode of action involving pore formation and lipid II binding such as nisin, subtilin, epidermin, gallidermin, and lacticin 3147 require additionally the presence of LanFEG.	INTRO
+90	94	LanI	protein_type	Although some lantibiotics such as Pep5, epicidin, epilancin, and lactocin S only require LanI for immunity, other lantibiotics with a dual mode of action involving pore formation and lipid II binding such as nisin, subtilin, epidermin, gallidermin, and lacticin 3147 require additionally the presence of LanFEG.	INTRO
+115	127	lantibiotics	chemical	Although some lantibiotics such as Pep5, epicidin, epilancin, and lactocin S only require LanI for immunity, other lantibiotics with a dual mode of action involving pore formation and lipid II binding such as nisin, subtilin, epidermin, gallidermin, and lacticin 3147 require additionally the presence of LanFEG.	INTRO
+209	214	nisin	chemical	Although some lantibiotics such as Pep5, epicidin, epilancin, and lactocin S only require LanI for immunity, other lantibiotics with a dual mode of action involving pore formation and lipid II binding such as nisin, subtilin, epidermin, gallidermin, and lacticin 3147 require additionally the presence of LanFEG.	INTRO
+216	224	subtilin	chemical	Although some lantibiotics such as Pep5, epicidin, epilancin, and lactocin S only require LanI for immunity, other lantibiotics with a dual mode of action involving pore formation and lipid II binding such as nisin, subtilin, epidermin, gallidermin, and lacticin 3147 require additionally the presence of LanFEG.	INTRO
+226	235	epidermin	chemical	Although some lantibiotics such as Pep5, epicidin, epilancin, and lactocin S only require LanI for immunity, other lantibiotics with a dual mode of action involving pore formation and lipid II binding such as nisin, subtilin, epidermin, gallidermin, and lacticin 3147 require additionally the presence of LanFEG.	INTRO
+237	248	gallidermin	chemical	Although some lantibiotics such as Pep5, epicidin, epilancin, and lactocin S only require LanI for immunity, other lantibiotics with a dual mode of action involving pore formation and lipid II binding such as nisin, subtilin, epidermin, gallidermin, and lacticin 3147 require additionally the presence of LanFEG.	INTRO
+254	267	lacticin 3147	chemical	Although some lantibiotics such as Pep5, epicidin, epilancin, and lactocin S only require LanI for immunity, other lantibiotics with a dual mode of action involving pore formation and lipid II binding such as nisin, subtilin, epidermin, gallidermin, and lacticin 3147 require additionally the presence of LanFEG.	INTRO
+305	311	LanFEG	protein_type	Although some lantibiotics such as Pep5, epicidin, epilancin, and lactocin S only require LanI for immunity, other lantibiotics with a dual mode of action involving pore formation and lipid II binding such as nisin, subtilin, epidermin, gallidermin, and lacticin 3147 require additionally the presence of LanFEG.	INTRO
+13	19	LanFEG	protein_type	Examples for LanFEG are NisI and NisFEG of the nisin system, SpaI and SpaFEG conferring immunity towards subtilin, and PepI constituting the immunity system of Pep5 producing strains.	INTRO
+24	28	NisI	protein	Examples for LanFEG are NisI and NisFEG of the nisin system, SpaI and SpaFEG conferring immunity towards subtilin, and PepI constituting the immunity system of Pep5 producing strains.	INTRO
+33	39	NisFEG	protein	Examples for LanFEG are NisI and NisFEG of the nisin system, SpaI and SpaFEG conferring immunity towards subtilin, and PepI constituting the immunity system of Pep5 producing strains.	INTRO
+47	52	nisin	chemical	Examples for LanFEG are NisI and NisFEG of the nisin system, SpaI and SpaFEG conferring immunity towards subtilin, and PepI constituting the immunity system of Pep5 producing strains.	INTRO
+61	65	SpaI	protein	Examples for LanFEG are NisI and NisFEG of the nisin system, SpaI and SpaFEG conferring immunity towards subtilin, and PepI constituting the immunity system of Pep5 producing strains.	INTRO
+70	76	SpaFEG	protein	Examples for LanFEG are NisI and NisFEG of the nisin system, SpaI and SpaFEG conferring immunity towards subtilin, and PepI constituting the immunity system of Pep5 producing strains.	INTRO
+105	113	subtilin	chemical	Examples for LanFEG are NisI and NisFEG of the nisin system, SpaI and SpaFEG conferring immunity towards subtilin, and PepI constituting the immunity system of Pep5 producing strains.	INTRO
+119	123	PepI	protein	Examples for LanFEG are NisI and NisFEG of the nisin system, SpaI and SpaFEG conferring immunity towards subtilin, and PepI constituting the immunity system of Pep5 producing strains.	INTRO
+160	164	Pep5	chemical	Examples for LanFEG are NisI and NisFEG of the nisin system, SpaI and SpaFEG conferring immunity towards subtilin, and PepI constituting the immunity system of Pep5 producing strains.	INTRO
+0	15	Structural data	evidence	Structural data are reported for the immunity proteins NisI from Lactococcus lactis, SpaI from Bacillus subtilis and MlbQ from the lantibiotic NAI-107 producer strain Microbispora ATCC PTA-5024.	INTRO
+37	54	immunity proteins	protein_type	Structural data are reported for the immunity proteins NisI from Lactococcus lactis, SpaI from Bacillus subtilis and MlbQ from the lantibiotic NAI-107 producer strain Microbispora ATCC PTA-5024.	INTRO
+55	59	NisI	protein	Structural data are reported for the immunity proteins NisI from Lactococcus lactis, SpaI from Bacillus subtilis and MlbQ from the lantibiotic NAI-107 producer strain Microbispora ATCC PTA-5024.	INTRO
+65	83	Lactococcus lactis	species	Structural data are reported for the immunity proteins NisI from Lactococcus lactis, SpaI from Bacillus subtilis and MlbQ from the lantibiotic NAI-107 producer strain Microbispora ATCC PTA-5024.	INTRO
+85	89	SpaI	protein	Structural data are reported for the immunity proteins NisI from Lactococcus lactis, SpaI from Bacillus subtilis and MlbQ from the lantibiotic NAI-107 producer strain Microbispora ATCC PTA-5024.	INTRO
+95	112	Bacillus subtilis	species	Structural data are reported for the immunity proteins NisI from Lactococcus lactis, SpaI from Bacillus subtilis and MlbQ from the lantibiotic NAI-107 producer strain Microbispora ATCC PTA-5024.	INTRO
+117	121	MlbQ	protein	Structural data are reported for the immunity proteins NisI from Lactococcus lactis, SpaI from Bacillus subtilis and MlbQ from the lantibiotic NAI-107 producer strain Microbispora ATCC PTA-5024.	INTRO
+131	142	lantibiotic	chemical	Structural data are reported for the immunity proteins NisI from Lactococcus lactis, SpaI from Bacillus subtilis and MlbQ from the lantibiotic NAI-107 producer strain Microbispora ATCC PTA-5024.	INTRO
+143	150	NAI-107	chemical	Structural data are reported for the immunity proteins NisI from Lactococcus lactis, SpaI from Bacillus subtilis and MlbQ from the lantibiotic NAI-107 producer strain Microbispora ATCC PTA-5024.	INTRO
+167	193	Microbispora ATCC PTA-5024	species	Structural data are reported for the immunity proteins NisI from Lactococcus lactis, SpaI from Bacillus subtilis and MlbQ from the lantibiotic NAI-107 producer strain Microbispora ATCC PTA-5024.	INTRO
+71	76	human	species	Recently, gene clusters were identified in certain clinically relevant human pathogenic strains such as Streptococcus agalactiae, S. aureus, and others that confer inherent resistance against specific lantibiotics such as nisin and resemble the genetic architecture of the lantibiotic immunity genes found in the producing strains.	INTRO
+104	128	Streptococcus agalactiae	species	Recently, gene clusters were identified in certain clinically relevant human pathogenic strains such as Streptococcus agalactiae, S. aureus, and others that confer inherent resistance against specific lantibiotics such as nisin and resemble the genetic architecture of the lantibiotic immunity genes found in the producing strains.	INTRO
+130	139	S. aureus	species	Recently, gene clusters were identified in certain clinically relevant human pathogenic strains such as Streptococcus agalactiae, S. aureus, and others that confer inherent resistance against specific lantibiotics such as nisin and resemble the genetic architecture of the lantibiotic immunity genes found in the producing strains.	INTRO
+201	213	lantibiotics	chemical	Recently, gene clusters were identified in certain clinically relevant human pathogenic strains such as Streptococcus agalactiae, S. aureus, and others that confer inherent resistance against specific lantibiotics such as nisin and resemble the genetic architecture of the lantibiotic immunity genes found in the producing strains.	INTRO
+222	227	nisin	chemical	Recently, gene clusters were identified in certain clinically relevant human pathogenic strains such as Streptococcus agalactiae, S. aureus, and others that confer inherent resistance against specific lantibiotics such as nisin and resemble the genetic architecture of the lantibiotic immunity genes found in the producing strains.	INTRO
+54	82	membrane-associated protease	protein_type	Within these resistance operons, genes encoding for a membrane-associated protease and an ABC transporter were identified.	INTRO
+90	105	ABC transporter	protein_type	Within these resistance operons, genes encoding for a membrane-associated protease and an ABC transporter were identified.	INTRO
+57	69	lantibiotics	chemical	Expression of these proteins provides resistance against lantibiotics.	INTRO
+14	23	structure	evidence	Recently, the structure of SaNSR from S. agalactiae was solved which provides resistance against nisin by a protease activity.	INTRO
+27	32	SaNSR	protein	Recently, the structure of SaNSR from S. agalactiae was solved which provides resistance against nisin by a protease activity.	INTRO
+38	51	S. agalactiae	species	Recently, the structure of SaNSR from S. agalactiae was solved which provides resistance against nisin by a protease activity.	INTRO
+97	102	nisin	chemical	Recently, the structure of SaNSR from S. agalactiae was solved which provides resistance against nisin by a protease activity.	INTRO
+71	91	two-component system	complex_assembly	Furthermore, the upregulation of these genes is mediated by a specific two-component system (TCS) similar to the one found in lantibiotic producing strains, consisting of a sensor histidine kinase (HK) and a response regulator (RR), apparently mediate the expression of the resistance proteins: HK senses the external lantibiotic and, upon receiving the stimuli, auto-phosphorylates at a conserved histidine residue within the cytosol; this high-energetic phosphoryl group is then transferred to the associated RR inducing a conformational change there, which activates the RR to evoke the cellular response.	INTRO
+93	96	TCS	complex_assembly	Furthermore, the upregulation of these genes is mediated by a specific two-component system (TCS) similar to the one found in lantibiotic producing strains, consisting of a sensor histidine kinase (HK) and a response regulator (RR), apparently mediate the expression of the resistance proteins: HK senses the external lantibiotic and, upon receiving the stimuli, auto-phosphorylates at a conserved histidine residue within the cytosol; this high-energetic phosphoryl group is then transferred to the associated RR inducing a conformational change there, which activates the RR to evoke the cellular response.	INTRO
+126	137	lantibiotic	chemical	Furthermore, the upregulation of these genes is mediated by a specific two-component system (TCS) similar to the one found in lantibiotic producing strains, consisting of a sensor histidine kinase (HK) and a response regulator (RR), apparently mediate the expression of the resistance proteins: HK senses the external lantibiotic and, upon receiving the stimuli, auto-phosphorylates at a conserved histidine residue within the cytosol; this high-energetic phosphoryl group is then transferred to the associated RR inducing a conformational change there, which activates the RR to evoke the cellular response.	INTRO
+180	196	histidine kinase	protein_type	Furthermore, the upregulation of these genes is mediated by a specific two-component system (TCS) similar to the one found in lantibiotic producing strains, consisting of a sensor histidine kinase (HK) and a response regulator (RR), apparently mediate the expression of the resistance proteins: HK senses the external lantibiotic and, upon receiving the stimuli, auto-phosphorylates at a conserved histidine residue within the cytosol; this high-energetic phosphoryl group is then transferred to the associated RR inducing a conformational change there, which activates the RR to evoke the cellular response.	INTRO
+198	200	HK	protein_type	Furthermore, the upregulation of these genes is mediated by a specific two-component system (TCS) similar to the one found in lantibiotic producing strains, consisting of a sensor histidine kinase (HK) and a response regulator (RR), apparently mediate the expression of the resistance proteins: HK senses the external lantibiotic and, upon receiving the stimuli, auto-phosphorylates at a conserved histidine residue within the cytosol; this high-energetic phosphoryl group is then transferred to the associated RR inducing a conformational change there, which activates the RR to evoke the cellular response.	INTRO
+208	226	response regulator	protein_type	Furthermore, the upregulation of these genes is mediated by a specific two-component system (TCS) similar to the one found in lantibiotic producing strains, consisting of a sensor histidine kinase (HK) and a response regulator (RR), apparently mediate the expression of the resistance proteins: HK senses the external lantibiotic and, upon receiving the stimuli, auto-phosphorylates at a conserved histidine residue within the cytosol; this high-energetic phosphoryl group is then transferred to the associated RR inducing a conformational change there, which activates the RR to evoke the cellular response.	INTRO
+228	230	RR	protein_type	Furthermore, the upregulation of these genes is mediated by a specific two-component system (TCS) similar to the one found in lantibiotic producing strains, consisting of a sensor histidine kinase (HK) and a response regulator (RR), apparently mediate the expression of the resistance proteins: HK senses the external lantibiotic and, upon receiving the stimuli, auto-phosphorylates at a conserved histidine residue within the cytosol; this high-energetic phosphoryl group is then transferred to the associated RR inducing a conformational change there, which activates the RR to evoke the cellular response.	INTRO
+295	297	HK	protein_type	Furthermore, the upregulation of these genes is mediated by a specific two-component system (TCS) similar to the one found in lantibiotic producing strains, consisting of a sensor histidine kinase (HK) and a response regulator (RR), apparently mediate the expression of the resistance proteins: HK senses the external lantibiotic and, upon receiving the stimuli, auto-phosphorylates at a conserved histidine residue within the cytosol; this high-energetic phosphoryl group is then transferred to the associated RR inducing a conformational change there, which activates the RR to evoke the cellular response.	INTRO
+318	329	lantibiotic	chemical	Furthermore, the upregulation of these genes is mediated by a specific two-component system (TCS) similar to the one found in lantibiotic producing strains, consisting of a sensor histidine kinase (HK) and a response regulator (RR), apparently mediate the expression of the resistance proteins: HK senses the external lantibiotic and, upon receiving the stimuli, auto-phosphorylates at a conserved histidine residue within the cytosol; this high-energetic phosphoryl group is then transferred to the associated RR inducing a conformational change there, which activates the RR to evoke the cellular response.	INTRO
+363	382	auto-phosphorylates	ptm	Furthermore, the upregulation of these genes is mediated by a specific two-component system (TCS) similar to the one found in lantibiotic producing strains, consisting of a sensor histidine kinase (HK) and a response regulator (RR), apparently mediate the expression of the resistance proteins: HK senses the external lantibiotic and, upon receiving the stimuli, auto-phosphorylates at a conserved histidine residue within the cytosol; this high-energetic phosphoryl group is then transferred to the associated RR inducing a conformational change there, which activates the RR to evoke the cellular response.	INTRO
+388	397	conserved	protein_state	Furthermore, the upregulation of these genes is mediated by a specific two-component system (TCS) similar to the one found in lantibiotic producing strains, consisting of a sensor histidine kinase (HK) and a response regulator (RR), apparently mediate the expression of the resistance proteins: HK senses the external lantibiotic and, upon receiving the stimuli, auto-phosphorylates at a conserved histidine residue within the cytosol; this high-energetic phosphoryl group is then transferred to the associated RR inducing a conformational change there, which activates the RR to evoke the cellular response.	INTRO
+398	407	histidine	residue_name	Furthermore, the upregulation of these genes is mediated by a specific two-component system (TCS) similar to the one found in lantibiotic producing strains, consisting of a sensor histidine kinase (HK) and a response regulator (RR), apparently mediate the expression of the resistance proteins: HK senses the external lantibiotic and, upon receiving the stimuli, auto-phosphorylates at a conserved histidine residue within the cytosol; this high-energetic phosphoryl group is then transferred to the associated RR inducing a conformational change there, which activates the RR to evoke the cellular response.	INTRO
+511	513	RR	protein_type	Furthermore, the upregulation of these genes is mediated by a specific two-component system (TCS) similar to the one found in lantibiotic producing strains, consisting of a sensor histidine kinase (HK) and a response regulator (RR), apparently mediate the expression of the resistance proteins: HK senses the external lantibiotic and, upon receiving the stimuli, auto-phosphorylates at a conserved histidine residue within the cytosol; this high-energetic phosphoryl group is then transferred to the associated RR inducing a conformational change there, which activates the RR to evoke the cellular response.	INTRO
+574	576	RR	protein_type	Furthermore, the upregulation of these genes is mediated by a specific two-component system (TCS) similar to the one found in lantibiotic producing strains, consisting of a sensor histidine kinase (HK) and a response regulator (RR), apparently mediate the expression of the resistance proteins: HK senses the external lantibiotic and, upon receiving the stimuli, auto-phosphorylates at a conserved histidine residue within the cytosol; this high-energetic phosphoryl group is then transferred to the associated RR inducing a conformational change there, which activates the RR to evoke the cellular response.	INTRO
+0	8	Bacteria	taxonomy_domain	Bacteria have the ability to sense and survive various environmental stimuli through adaptive responses, which are regulated by TCSs.	INTRO
+128	132	TCSs	complex_assembly	Bacteria have the ability to sense and survive various environmental stimuli through adaptive responses, which are regulated by TCSs.	INTRO
+4	14	absence of	protein_state	The absence of TCSs within mammals makes them unique targets for novel antimicrobial drugs.	INTRO
+15	19	TCSs	complex_assembly	The absence of TCSs within mammals makes them unique targets for novel antimicrobial drugs.	INTRO
+27	34	mammals	taxonomy_domain	The absence of TCSs within mammals makes them unique targets for novel antimicrobial drugs.	INTRO
+22	33	lantibiotic	chemical	The expression of the lantibiotic-resistance genes via TCS is generally regulated by microorganism-specific lantibiotics, which act via external stimuli.	INTRO
+55	58	TCS	complex_assembly	The expression of the lantibiotic-resistance genes via TCS is generally regulated by microorganism-specific lantibiotics, which act via external stimuli.	INTRO
+108	120	lantibiotics	chemical	The expression of the lantibiotic-resistance genes via TCS is generally regulated by microorganism-specific lantibiotics, which act via external stimuli.	INTRO
+17	20	TCS	complex_assembly	Some examples of TCS are: BraRS in S. aureus which is induced by bacitracin, nisin and nukacin-ISK-1 resistance, BceRS in Bacillus spp. that is induced by actagardine and mersacidin resistance, LcrRS in Streptococcus mutans induced by nukacin-ISK-1 and lacticin 481 and LisRK of Listeria monocytogenes induced by nisin resistance.	INTRO
+26	31	BraRS	protein	Some examples of TCS are: BraRS in S. aureus which is induced by bacitracin, nisin and nukacin-ISK-1 resistance, BceRS in Bacillus spp. that is induced by actagardine and mersacidin resistance, LcrRS in Streptococcus mutans induced by nukacin-ISK-1 and lacticin 481 and LisRK of Listeria monocytogenes induced by nisin resistance.	INTRO
+35	44	S. aureus	species	Some examples of TCS are: BraRS in S. aureus which is induced by bacitracin, nisin and nukacin-ISK-1 resistance, BceRS in Bacillus spp. that is induced by actagardine and mersacidin resistance, LcrRS in Streptococcus mutans induced by nukacin-ISK-1 and lacticin 481 and LisRK of Listeria monocytogenes induced by nisin resistance.	INTRO
+65	75	bacitracin	chemical	Some examples of TCS are: BraRS in S. aureus which is induced by bacitracin, nisin and nukacin-ISK-1 resistance, BceRS in Bacillus spp. that is induced by actagardine and mersacidin resistance, LcrRS in Streptococcus mutans induced by nukacin-ISK-1 and lacticin 481 and LisRK of Listeria monocytogenes induced by nisin resistance.	INTRO
+77	82	nisin	chemical	Some examples of TCS are: BraRS in S. aureus which is induced by bacitracin, nisin and nukacin-ISK-1 resistance, BceRS in Bacillus spp. that is induced by actagardine and mersacidin resistance, LcrRS in Streptococcus mutans induced by nukacin-ISK-1 and lacticin 481 and LisRK of Listeria monocytogenes induced by nisin resistance.	INTRO
+87	100	nukacin-ISK-1	chemical	Some examples of TCS are: BraRS in S. aureus which is induced by bacitracin, nisin and nukacin-ISK-1 resistance, BceRS in Bacillus spp. that is induced by actagardine and mersacidin resistance, LcrRS in Streptococcus mutans induced by nukacin-ISK-1 and lacticin 481 and LisRK of Listeria monocytogenes induced by nisin resistance.	INTRO
+113	118	BceRS	protein	Some examples of TCS are: BraRS in S. aureus which is induced by bacitracin, nisin and nukacin-ISK-1 resistance, BceRS in Bacillus spp. that is induced by actagardine and mersacidin resistance, LcrRS in Streptococcus mutans induced by nukacin-ISK-1 and lacticin 481 and LisRK of Listeria monocytogenes induced by nisin resistance.	INTRO
+122	134	Bacillus spp	taxonomy_domain	Some examples of TCS are: BraRS in S. aureus which is induced by bacitracin, nisin and nukacin-ISK-1 resistance, BceRS in Bacillus spp. that is induced by actagardine and mersacidin resistance, LcrRS in Streptococcus mutans induced by nukacin-ISK-1 and lacticin 481 and LisRK of Listeria monocytogenes induced by nisin resistance.	INTRO
+155	166	actagardine	chemical	Some examples of TCS are: BraRS in S. aureus which is induced by bacitracin, nisin and nukacin-ISK-1 resistance, BceRS in Bacillus spp. that is induced by actagardine and mersacidin resistance, LcrRS in Streptococcus mutans induced by nukacin-ISK-1 and lacticin 481 and LisRK of Listeria monocytogenes induced by nisin resistance.	INTRO
+171	181	mersacidin	chemical	Some examples of TCS are: BraRS in S. aureus which is induced by bacitracin, nisin and nukacin-ISK-1 resistance, BceRS in Bacillus spp. that is induced by actagardine and mersacidin resistance, LcrRS in Streptococcus mutans induced by nukacin-ISK-1 and lacticin 481 and LisRK of Listeria monocytogenes induced by nisin resistance.	INTRO
+194	199	LcrRS	protein	Some examples of TCS are: BraRS in S. aureus which is induced by bacitracin, nisin and nukacin-ISK-1 resistance, BceRS in Bacillus spp. that is induced by actagardine and mersacidin resistance, LcrRS in Streptococcus mutans induced by nukacin-ISK-1 and lacticin 481 and LisRK of Listeria monocytogenes induced by nisin resistance.	INTRO
+203	223	Streptococcus mutans	species	Some examples of TCS are: BraRS in S. aureus which is induced by bacitracin, nisin and nukacin-ISK-1 resistance, BceRS in Bacillus spp. that is induced by actagardine and mersacidin resistance, LcrRS in Streptococcus mutans induced by nukacin-ISK-1 and lacticin 481 and LisRK of Listeria monocytogenes induced by nisin resistance.	INTRO
+235	248	nukacin-ISK-1	chemical	Some examples of TCS are: BraRS in S. aureus which is induced by bacitracin, nisin and nukacin-ISK-1 resistance, BceRS in Bacillus spp. that is induced by actagardine and mersacidin resistance, LcrRS in Streptococcus mutans induced by nukacin-ISK-1 and lacticin 481 and LisRK of Listeria monocytogenes induced by nisin resistance.	INTRO
+253	265	lacticin 481	chemical	Some examples of TCS are: BraRS in S. aureus which is induced by bacitracin, nisin and nukacin-ISK-1 resistance, BceRS in Bacillus spp. that is induced by actagardine and mersacidin resistance, LcrRS in Streptococcus mutans induced by nukacin-ISK-1 and lacticin 481 and LisRK of Listeria monocytogenes induced by nisin resistance.	INTRO
+270	275	LisRK	protein	Some examples of TCS are: BraRS in S. aureus which is induced by bacitracin, nisin and nukacin-ISK-1 resistance, BceRS in Bacillus spp. that is induced by actagardine and mersacidin resistance, LcrRS in Streptococcus mutans induced by nukacin-ISK-1 and lacticin 481 and LisRK of Listeria monocytogenes induced by nisin resistance.	INTRO
+279	301	Listeria monocytogenes	species	Some examples of TCS are: BraRS in S. aureus which is induced by bacitracin, nisin and nukacin-ISK-1 resistance, BceRS in Bacillus spp. that is induced by actagardine and mersacidin resistance, LcrRS in Streptococcus mutans induced by nukacin-ISK-1 and lacticin 481 and LisRK of Listeria monocytogenes induced by nisin resistance.	INTRO
+313	318	nisin	chemical	Some examples of TCS are: BraRS in S. aureus which is induced by bacitracin, nisin and nukacin-ISK-1 resistance, BceRS in Bacillus spp. that is induced by actagardine and mersacidin resistance, LcrRS in Streptococcus mutans induced by nukacin-ISK-1 and lacticin 481 and LisRK of Listeria monocytogenes induced by nisin resistance.	INTRO
+22	34	lantibiotics	chemical	Furthermore, multiple lantibiotics can induce the TCS CprRK from Clostridium difficile, leading to the expression of the genes localized on the cpr operon, resulting in resistance against several lantibiotics of which nisin, gallidermin, subtilin, and mutacin 1140 are some examples.	INTRO
+50	53	TCS	complex_assembly	Furthermore, multiple lantibiotics can induce the TCS CprRK from Clostridium difficile, leading to the expression of the genes localized on the cpr operon, resulting in resistance against several lantibiotics of which nisin, gallidermin, subtilin, and mutacin 1140 are some examples.	INTRO
+54	59	CprRK	protein	Furthermore, multiple lantibiotics can induce the TCS CprRK from Clostridium difficile, leading to the expression of the genes localized on the cpr operon, resulting in resistance against several lantibiotics of which nisin, gallidermin, subtilin, and mutacin 1140 are some examples.	INTRO
+65	86	Clostridium difficile	species	Furthermore, multiple lantibiotics can induce the TCS CprRK from Clostridium difficile, leading to the expression of the genes localized on the cpr operon, resulting in resistance against several lantibiotics of which nisin, gallidermin, subtilin, and mutacin 1140 are some examples.	INTRO
+144	147	cpr	gene	Furthermore, multiple lantibiotics can induce the TCS CprRK from Clostridium difficile, leading to the expression of the genes localized on the cpr operon, resulting in resistance against several lantibiotics of which nisin, gallidermin, subtilin, and mutacin 1140 are some examples.	INTRO
+196	208	lantibiotics	chemical	Furthermore, multiple lantibiotics can induce the TCS CprRK from Clostridium difficile, leading to the expression of the genes localized on the cpr operon, resulting in resistance against several lantibiotics of which nisin, gallidermin, subtilin, and mutacin 1140 are some examples.	INTRO
+218	223	nisin	chemical	Furthermore, multiple lantibiotics can induce the TCS CprRK from Clostridium difficile, leading to the expression of the genes localized on the cpr operon, resulting in resistance against several lantibiotics of which nisin, gallidermin, subtilin, and mutacin 1140 are some examples.	INTRO
+225	236	gallidermin	chemical	Furthermore, multiple lantibiotics can induce the TCS CprRK from Clostridium difficile, leading to the expression of the genes localized on the cpr operon, resulting in resistance against several lantibiotics of which nisin, gallidermin, subtilin, and mutacin 1140 are some examples.	INTRO
+238	246	subtilin	chemical	Furthermore, multiple lantibiotics can induce the TCS CprRK from Clostridium difficile, leading to the expression of the genes localized on the cpr operon, resulting in resistance against several lantibiotics of which nisin, gallidermin, subtilin, and mutacin 1140 are some examples.	INTRO
+252	264	mutacin 1140	chemical	Furthermore, multiple lantibiotics can induce the TCS CprRK from Clostridium difficile, leading to the expression of the genes localized on the cpr operon, resulting in resistance against several lantibiotics of which nisin, gallidermin, subtilin, and mutacin 1140 are some examples.	INTRO
+19	35	histidine kinase	protein_type	Interestingly, the histidine kinase contains two-transmembrane helices but lacks an extracellular sensory domain, and are therefore known as ‘intramembrane-sensing’ histidine kinases.	INTRO
+45	70	two-transmembrane helices	structure_element	Interestingly, the histidine kinase contains two-transmembrane helices but lacks an extracellular sensory domain, and are therefore known as ‘intramembrane-sensing’ histidine kinases.	INTRO
+84	112	extracellular sensory domain	structure_element	Interestingly, the histidine kinase contains two-transmembrane helices but lacks an extracellular sensory domain, and are therefore known as ‘intramembrane-sensing’ histidine kinases.	INTRO
+141	182	‘intramembrane-sensing’ histidine kinases	protein_type	Interestingly, the histidine kinase contains two-transmembrane helices but lacks an extracellular sensory domain, and are therefore known as ‘intramembrane-sensing’ histidine kinases.	INTRO
+80	92	lantibiotics	chemical	It has been suggested that in addition to conferring general resistance against lantibiotics, the BceAB-type transporters assist in signalling as via the presence of a large extracellular domain within the transmembrane segment indicated by experimental evidence from various systems.	INTRO
+98	121	BceAB-type transporters	protein_type	It has been suggested that in addition to conferring general resistance against lantibiotics, the BceAB-type transporters assist in signalling as via the presence of a large extracellular domain within the transmembrane segment indicated by experimental evidence from various systems.	INTRO
+174	194	extracellular domain	structure_element	It has been suggested that in addition to conferring general resistance against lantibiotics, the BceAB-type transporters assist in signalling as via the presence of a large extracellular domain within the transmembrane segment indicated by experimental evidence from various systems.	INTRO
+206	227	transmembrane segment	structure_element	It has been suggested that in addition to conferring general resistance against lantibiotics, the BceAB-type transporters assist in signalling as via the presence of a large extracellular domain within the transmembrane segment indicated by experimental evidence from various systems.	INTRO
+24	27	nsr	gene	The recently discovered nsr gene cluster of the human pathogen S. agalactiae encodes for the resistance protein NSR and the ABC transporter NsrFP, both conferring resistance against nisin.	INTRO
+48	53	human	species	The recently discovered nsr gene cluster of the human pathogen S. agalactiae encodes for the resistance protein NSR and the ABC transporter NsrFP, both conferring resistance against nisin.	INTRO
+63	76	S. agalactiae	species	The recently discovered nsr gene cluster of the human pathogen S. agalactiae encodes for the resistance protein NSR and the ABC transporter NsrFP, both conferring resistance against nisin.	INTRO
+93	111	resistance protein	protein_type	The recently discovered nsr gene cluster of the human pathogen S. agalactiae encodes for the resistance protein NSR and the ABC transporter NsrFP, both conferring resistance against nisin.	INTRO
+112	115	NSR	protein	The recently discovered nsr gene cluster of the human pathogen S. agalactiae encodes for the resistance protein NSR and the ABC transporter NsrFP, both conferring resistance against nisin.	INTRO
+124	139	ABC transporter	protein_type	The recently discovered nsr gene cluster of the human pathogen S. agalactiae encodes for the resistance protein NSR and the ABC transporter NsrFP, both conferring resistance against nisin.	INTRO
+140	145	NsrFP	protein	The recently discovered nsr gene cluster of the human pathogen S. agalactiae encodes for the resistance protein NSR and the ABC transporter NsrFP, both conferring resistance against nisin.	INTRO
+182	187	nisin	chemical	The recently discovered nsr gene cluster of the human pathogen S. agalactiae encodes for the resistance protein NSR and the ABC transporter NsrFP, both conferring resistance against nisin.	INTRO
+51	56	human	species	Homologous operons have been identified in various human pathogenic strains such as Staphylococcus epidermis and Streptococcus ictaluri based on the high sequence identity of NSR and NsrFP.	INTRO
+84	108	Staphylococcus epidermis	species	Homologous operons have been identified in various human pathogenic strains such as Staphylococcus epidermis and Streptococcus ictaluri based on the high sequence identity of NSR and NsrFP.	INTRO
+113	135	Streptococcus ictaluri	species	Homologous operons have been identified in various human pathogenic strains such as Staphylococcus epidermis and Streptococcus ictaluri based on the high sequence identity of NSR and NsrFP.	INTRO
+175	178	NSR	protein	Homologous operons have been identified in various human pathogenic strains such as Staphylococcus epidermis and Streptococcus ictaluri based on the high sequence identity of NSR and NsrFP.	INTRO
+183	188	NsrFP	protein	Homologous operons have been identified in various human pathogenic strains such as Staphylococcus epidermis and Streptococcus ictaluri based on the high sequence identity of NSR and NsrFP.	INTRO
+26	29	TCS	complex_assembly	In this gene cluster, the TCS NsrRK is responsible for the expression of the nsr and nsrFP genes.	INTRO
+30	35	NsrRK	protein	In this gene cluster, the TCS NsrRK is responsible for the expression of the nsr and nsrFP genes.	INTRO
+77	80	nsr	gene	In this gene cluster, the TCS NsrRK is responsible for the expression of the nsr and nsrFP genes.	INTRO
+85	90	nsrFP	gene	In this gene cluster, the TCS NsrRK is responsible for the expression of the nsr and nsrFP genes.	INTRO
+22	25	TCS	complex_assembly	The similarity of the TCS within all the described nisin resistance operons suggests an expression specifically induced by nisin.	INTRO
+51	56	nisin	chemical	The similarity of the TCS within all the described nisin resistance operons suggests an expression specifically induced by nisin.	INTRO
+123	128	nisin	chemical	The similarity of the TCS within all the described nisin resistance operons suggests an expression specifically induced by nisin.	INTRO
+6	11	NsrRK	protein	Thus, NsrRK might be a useful target to combat inherently pathogenic lantibiotic-resistant strains.	INTRO
+69	80	lantibiotic	chemical	Thus, NsrRK might be a useful target to combat inherently pathogenic lantibiotic-resistant strains.	INTRO
+11	14	RRs	protein_type	Generally, RRs consist of two distinct structural domains, a receiver domain (RD) and an effector domain (ED), that are separated from each other by a flexible linker.	INTRO
+61	76	receiver domain	structure_element	Generally, RRs consist of two distinct structural domains, a receiver domain (RD) and an effector domain (ED), that are separated from each other by a flexible linker.	INTRO
+78	80	RD	structure_element	Generally, RRs consist of two distinct structural domains, a receiver domain (RD) and an effector domain (ED), that are separated from each other by a flexible linker.	INTRO
+89	104	effector domain	structure_element	Generally, RRs consist of two distinct structural domains, a receiver domain (RD) and an effector domain (ED), that are separated from each other by a flexible linker.	INTRO
+106	108	ED	structure_element	Generally, RRs consist of two distinct structural domains, a receiver domain (RD) and an effector domain (ED), that are separated from each other by a flexible linker.	INTRO
+151	159	flexible	protein_state	Generally, RRs consist of two distinct structural domains, a receiver domain (RD) and an effector domain (ED), that are separated from each other by a flexible linker.	INTRO
+160	166	linker	structure_element	Generally, RRs consist of two distinct structural domains, a receiver domain (RD) and an effector domain (ED), that are separated from each other by a flexible linker.	INTRO
+0	3	RDs	structure_element	RDs contain a highly conserved aspartate residue, which acts as a phosphoryl acceptor that becomes phosphorylated by the kinase domain of the histidine kinase upon reception of an external signal.	INTRO
+14	30	highly conserved	protein_state	RDs contain a highly conserved aspartate residue, which acts as a phosphoryl acceptor that becomes phosphorylated by the kinase domain of the histidine kinase upon reception of an external signal.	INTRO
+31	40	aspartate	residue_name	RDs contain a highly conserved aspartate residue, which acts as a phosphoryl acceptor that becomes phosphorylated by the kinase domain of the histidine kinase upon reception of an external signal.	INTRO
+99	113	phosphorylated	protein_state	RDs contain a highly conserved aspartate residue, which acts as a phosphoryl acceptor that becomes phosphorylated by the kinase domain of the histidine kinase upon reception of an external signal.	INTRO
+121	134	kinase domain	structure_element	RDs contain a highly conserved aspartate residue, which acts as a phosphoryl acceptor that becomes phosphorylated by the kinase domain of the histidine kinase upon reception of an external signal.	INTRO
+142	158	histidine kinase	protein_type	RDs contain a highly conserved aspartate residue, which acts as a phosphoryl acceptor that becomes phosphorylated by the kinase domain of the histidine kinase upon reception of an external signal.	INTRO
+4	6	ED	structure_element	The ED is thereby activated and binds to the designated promoters, thus initiating transcription of the target genes.	INTRO
+4	7	RRs	protein_type	The RRs are classified into different subfamilies depending on the three-dimensional structure of their EDs.	INTRO
+104	107	EDs	structure_element	The RRs are classified into different subfamilies depending on the three-dimensional structure of their EDs.	INTRO
+4	23	OmpR/PhoB subfamily	protein_type	The OmpR/PhoB subfamily is the largest subgroup of RRs and comprises approximately 40% of all response regulators in bacteria.	INTRO
+51	54	RRs	protein_type	The OmpR/PhoB subfamily is the largest subgroup of RRs and comprises approximately 40% of all response regulators in bacteria.	INTRO
+94	113	response regulators	protein_type	The OmpR/PhoB subfamily is the largest subgroup of RRs and comprises approximately 40% of all response regulators in bacteria.	INTRO
+117	125	bacteria	taxonomy_domain	The OmpR/PhoB subfamily is the largest subgroup of RRs and comprises approximately 40% of all response regulators in bacteria.	INTRO
+41	64	winged helix-turn-helix	structure_element	All their members are characterized by a winged helix-turn-helix (wHTH) motif.	INTRO
+66	70	wHTH	structure_element	All their members are characterized by a winged helix-turn-helix (wHTH) motif.	INTRO
+18	28	structures	evidence	Although numerous structures of the single domains are known, only a few structures of full-length OmpR/PhoB-type RRs have been determined: RegX3 (PDB code: 2OQR), MtrA (PDB code: 2GWR), PrrA (PDB code: 1YS6) and PhoP (PDB code: 3R0J) from Mycobacterium tuberculosis; DrrB (PDB code: 1P2F) and DrrD (PDB code: 1KGS) from Thermotoga maritima; and KdpE from Escherichia coli (PDB code: 4KNY).	INTRO
+73	83	structures	evidence	Although numerous structures of the single domains are known, only a few structures of full-length OmpR/PhoB-type RRs have been determined: RegX3 (PDB code: 2OQR), MtrA (PDB code: 2GWR), PrrA (PDB code: 1YS6) and PhoP (PDB code: 3R0J) from Mycobacterium tuberculosis; DrrB (PDB code: 1P2F) and DrrD (PDB code: 1KGS) from Thermotoga maritima; and KdpE from Escherichia coli (PDB code: 4KNY).	INTRO
+87	98	full-length	protein_state	Although numerous structures of the single domains are known, only a few structures of full-length OmpR/PhoB-type RRs have been determined: RegX3 (PDB code: 2OQR), MtrA (PDB code: 2GWR), PrrA (PDB code: 1YS6) and PhoP (PDB code: 3R0J) from Mycobacterium tuberculosis; DrrB (PDB code: 1P2F) and DrrD (PDB code: 1KGS) from Thermotoga maritima; and KdpE from Escherichia coli (PDB code: 4KNY).	INTRO
+99	117	OmpR/PhoB-type RRs	protein_type	Although numerous structures of the single domains are known, only a few structures of full-length OmpR/PhoB-type RRs have been determined: RegX3 (PDB code: 2OQR), MtrA (PDB code: 2GWR), PrrA (PDB code: 1YS6) and PhoP (PDB code: 3R0J) from Mycobacterium tuberculosis; DrrB (PDB code: 1P2F) and DrrD (PDB code: 1KGS) from Thermotoga maritima; and KdpE from Escherichia coli (PDB code: 4KNY).	INTRO
+140	145	RegX3	protein	Although numerous structures of the single domains are known, only a few structures of full-length OmpR/PhoB-type RRs have been determined: RegX3 (PDB code: 2OQR), MtrA (PDB code: 2GWR), PrrA (PDB code: 1YS6) and PhoP (PDB code: 3R0J) from Mycobacterium tuberculosis; DrrB (PDB code: 1P2F) and DrrD (PDB code: 1KGS) from Thermotoga maritima; and KdpE from Escherichia coli (PDB code: 4KNY).	INTRO
+164	168	MtrA	protein	Although numerous structures of the single domains are known, only a few structures of full-length OmpR/PhoB-type RRs have been determined: RegX3 (PDB code: 2OQR), MtrA (PDB code: 2GWR), PrrA (PDB code: 1YS6) and PhoP (PDB code: 3R0J) from Mycobacterium tuberculosis; DrrB (PDB code: 1P2F) and DrrD (PDB code: 1KGS) from Thermotoga maritima; and KdpE from Escherichia coli (PDB code: 4KNY).	INTRO
+187	191	PrrA	protein	Although numerous structures of the single domains are known, only a few structures of full-length OmpR/PhoB-type RRs have been determined: RegX3 (PDB code: 2OQR), MtrA (PDB code: 2GWR), PrrA (PDB code: 1YS6) and PhoP (PDB code: 3R0J) from Mycobacterium tuberculosis; DrrB (PDB code: 1P2F) and DrrD (PDB code: 1KGS) from Thermotoga maritima; and KdpE from Escherichia coli (PDB code: 4KNY).	INTRO
+213	217	PhoP	protein	Although numerous structures of the single domains are known, only a few structures of full-length OmpR/PhoB-type RRs have been determined: RegX3 (PDB code: 2OQR), MtrA (PDB code: 2GWR), PrrA (PDB code: 1YS6) and PhoP (PDB code: 3R0J) from Mycobacterium tuberculosis; DrrB (PDB code: 1P2F) and DrrD (PDB code: 1KGS) from Thermotoga maritima; and KdpE from Escherichia coli (PDB code: 4KNY).	INTRO
+240	266	Mycobacterium tuberculosis	species	Although numerous structures of the single domains are known, only a few structures of full-length OmpR/PhoB-type RRs have been determined: RegX3 (PDB code: 2OQR), MtrA (PDB code: 2GWR), PrrA (PDB code: 1YS6) and PhoP (PDB code: 3R0J) from Mycobacterium tuberculosis; DrrB (PDB code: 1P2F) and DrrD (PDB code: 1KGS) from Thermotoga maritima; and KdpE from Escherichia coli (PDB code: 4KNY).	INTRO
+268	272	DrrB	protein	Although numerous structures of the single domains are known, only a few structures of full-length OmpR/PhoB-type RRs have been determined: RegX3 (PDB code: 2OQR), MtrA (PDB code: 2GWR), PrrA (PDB code: 1YS6) and PhoP (PDB code: 3R0J) from Mycobacterium tuberculosis; DrrB (PDB code: 1P2F) and DrrD (PDB code: 1KGS) from Thermotoga maritima; and KdpE from Escherichia coli (PDB code: 4KNY).	INTRO
+294	298	DrrD	protein	Although numerous structures of the single domains are known, only a few structures of full-length OmpR/PhoB-type RRs have been determined: RegX3 (PDB code: 2OQR), MtrA (PDB code: 2GWR), PrrA (PDB code: 1YS6) and PhoP (PDB code: 3R0J) from Mycobacterium tuberculosis; DrrB (PDB code: 1P2F) and DrrD (PDB code: 1KGS) from Thermotoga maritima; and KdpE from Escherichia coli (PDB code: 4KNY).	INTRO
+321	340	Thermotoga maritima	species	Although numerous structures of the single domains are known, only a few structures of full-length OmpR/PhoB-type RRs have been determined: RegX3 (PDB code: 2OQR), MtrA (PDB code: 2GWR), PrrA (PDB code: 1YS6) and PhoP (PDB code: 3R0J) from Mycobacterium tuberculosis; DrrB (PDB code: 1P2F) and DrrD (PDB code: 1KGS) from Thermotoga maritima; and KdpE from Escherichia coli (PDB code: 4KNY).	INTRO
+346	350	KdpE	protein	Although numerous structures of the single domains are known, only a few structures of full-length OmpR/PhoB-type RRs have been determined: RegX3 (PDB code: 2OQR), MtrA (PDB code: 2GWR), PrrA (PDB code: 1YS6) and PhoP (PDB code: 3R0J) from Mycobacterium tuberculosis; DrrB (PDB code: 1P2F) and DrrD (PDB code: 1KGS) from Thermotoga maritima; and KdpE from Escherichia coli (PDB code: 4KNY).	INTRO
+356	372	Escherichia coli	species	Although numerous structures of the single domains are known, only a few structures of full-length OmpR/PhoB-type RRs have been determined: RegX3 (PDB code: 2OQR), MtrA (PDB code: 2GWR), PrrA (PDB code: 1YS6) and PhoP (PDB code: 3R0J) from Mycobacterium tuberculosis; DrrB (PDB code: 1P2F) and DrrD (PDB code: 1KGS) from Thermotoga maritima; and KdpE from Escherichia coli (PDB code: 4KNY).	INTRO
+12	22	structures	evidence	The various structures of RRs reveal that in addition to being in either “inactive” or “active” state, the RRs can also exist in two distinct conformations: “open” and “closed”.	INTRO
+26	29	RRs	protein_type	The various structures of RRs reveal that in addition to being in either “inactive” or “active” state, the RRs can also exist in two distinct conformations: “open” and “closed”.	INTRO
+74	82	inactive	protein_state	The various structures of RRs reveal that in addition to being in either “inactive” or “active” state, the RRs can also exist in two distinct conformations: “open” and “closed”.	INTRO
+88	94	active	protein_state	The various structures of RRs reveal that in addition to being in either “inactive” or “active” state, the RRs can also exist in two distinct conformations: “open” and “closed”.	INTRO
+107	110	RRs	protein_type	The various structures of RRs reveal that in addition to being in either “inactive” or “active” state, the RRs can also exist in two distinct conformations: “open” and “closed”.	INTRO
+158	162	open	protein_state	The various structures of RRs reveal that in addition to being in either “inactive” or “active” state, the RRs can also exist in two distinct conformations: “open” and “closed”.	INTRO
+169	175	closed	protein_state	The various structures of RRs reveal that in addition to being in either “inactive” or “active” state, the RRs can also exist in two distinct conformations: “open” and “closed”.	INTRO
+0	4	MtrA	protein	MtrA and PrrA exhibit a very compact, closed structure with the DNA-binding sequence, called recognition helix, of the ED being inaccessible to DNA.	INTRO
+9	13	PrrA	protein	MtrA and PrrA exhibit a very compact, closed structure with the DNA-binding sequence, called recognition helix, of the ED being inaccessible to DNA.	INTRO
+24	36	very compact	protein_state	MtrA and PrrA exhibit a very compact, closed structure with the DNA-binding sequence, called recognition helix, of the ED being inaccessible to DNA.	INTRO
+38	44	closed	protein_state	MtrA and PrrA exhibit a very compact, closed structure with the DNA-binding sequence, called recognition helix, of the ED being inaccessible to DNA.	INTRO
+45	54	structure	evidence	MtrA and PrrA exhibit a very compact, closed structure with the DNA-binding sequence, called recognition helix, of the ED being inaccessible to DNA.	INTRO
+64	84	DNA-binding sequence	structure_element	MtrA and PrrA exhibit a very compact, closed structure with the DNA-binding sequence, called recognition helix, of the ED being inaccessible to DNA.	INTRO
+93	110	recognition helix	structure_element	MtrA and PrrA exhibit a very compact, closed structure with the DNA-binding sequence, called recognition helix, of the ED being inaccessible to DNA.	INTRO
+119	121	ED	structure_element	MtrA and PrrA exhibit a very compact, closed structure with the DNA-binding sequence, called recognition helix, of the ED being inaccessible to DNA.	INTRO
+144	147	DNA	chemical	MtrA and PrrA exhibit a very compact, closed structure with the DNA-binding sequence, called recognition helix, of the ED being inaccessible to DNA.	INTRO
+4	14	structures	evidence	The structures of DrrD and DrrB exist in an open conformation, here the recognition helix is fully exposed, suggesting that RRs are flexible in solution and can adopt multiple conformations.	INTRO
+18	22	DrrD	protein	The structures of DrrD and DrrB exist in an open conformation, here the recognition helix is fully exposed, suggesting that RRs are flexible in solution and can adopt multiple conformations.	INTRO
+27	31	DrrB	protein	The structures of DrrD and DrrB exist in an open conformation, here the recognition helix is fully exposed, suggesting that RRs are flexible in solution and can adopt multiple conformations.	INTRO
+44	48	open	protein_state	The structures of DrrD and DrrB exist in an open conformation, here the recognition helix is fully exposed, suggesting that RRs are flexible in solution and can adopt multiple conformations.	INTRO
+72	89	recognition helix	structure_element	The structures of DrrD and DrrB exist in an open conformation, here the recognition helix is fully exposed, suggesting that RRs are flexible in solution and can adopt multiple conformations.	INTRO
+93	106	fully exposed	protein_state	The structures of DrrD and DrrB exist in an open conformation, here the recognition helix is fully exposed, suggesting that RRs are flexible in solution and can adopt multiple conformations.	INTRO
+124	127	RRs	protein_type	The structures of DrrD and DrrB exist in an open conformation, here the recognition helix is fully exposed, suggesting that RRs are flexible in solution and can adopt multiple conformations.	INTRO
+132	140	flexible	protein_state	The structures of DrrD and DrrB exist in an open conformation, here the recognition helix is fully exposed, suggesting that RRs are flexible in solution and can adopt multiple conformations.	INTRO
+22	40	crystal structures	evidence	Here, we describe the crystal structures of the N-terminal RD and the C-terminal ED of the lantibiotic resistance-associated RR NsrR from S. agalactiae.	INTRO
+59	61	RD	structure_element	Here, we describe the crystal structures of the N-terminal RD and the C-terminal ED of the lantibiotic resistance-associated RR NsrR from S. agalactiae.	INTRO
+81	83	ED	structure_element	Here, we describe the crystal structures of the N-terminal RD and the C-terminal ED of the lantibiotic resistance-associated RR NsrR from S. agalactiae.	INTRO
+91	127	lantibiotic resistance-associated RR	protein_type	Here, we describe the crystal structures of the N-terminal RD and the C-terminal ED of the lantibiotic resistance-associated RR NsrR from S. agalactiae.	INTRO
+128	132	NsrR	protein	Here, we describe the crystal structures of the N-terminal RD and the C-terminal ED of the lantibiotic resistance-associated RR NsrR from S. agalactiae.	INTRO
+138	151	S. agalactiae	species	Here, we describe the crystal structures of the N-terminal RD and the C-terminal ED of the lantibiotic resistance-associated RR NsrR from S. agalactiae.	INTRO
+0	4	NsrR	protein	NsrR is part of the nisin resistance operon.	INTRO
+20	25	nisin	chemical	NsrR is part of the nisin resistance operon.	INTRO
+59	62	TCS	complex_assembly	The expression of the genes of this operon is induced by a TCS consisting of the HK NsrK and the RR NsrR. Based on the crystal structures of both the domains, modeling was employed to shed light on the putative DNA-bound state of full-length NsrR.	INTRO
+81	83	HK	protein_type	The expression of the genes of this operon is induced by a TCS consisting of the HK NsrK and the RR NsrR. Based on the crystal structures of both the domains, modeling was employed to shed light on the putative DNA-bound state of full-length NsrR.	INTRO
+84	88	NsrK	protein	The expression of the genes of this operon is induced by a TCS consisting of the HK NsrK and the RR NsrR. Based on the crystal structures of both the domains, modeling was employed to shed light on the putative DNA-bound state of full-length NsrR.	INTRO
+97	99	RR	protein_type	The expression of the genes of this operon is induced by a TCS consisting of the HK NsrK and the RR NsrR. Based on the crystal structures of both the domains, modeling was employed to shed light on the putative DNA-bound state of full-length NsrR.	INTRO
+100	104	NsrR	protein	The expression of the genes of this operon is induced by a TCS consisting of the HK NsrK and the RR NsrR. Based on the crystal structures of both the domains, modeling was employed to shed light on the putative DNA-bound state of full-length NsrR.	INTRO
+119	137	crystal structures	evidence	The expression of the genes of this operon is induced by a TCS consisting of the HK NsrK and the RR NsrR. Based on the crystal structures of both the domains, modeling was employed to shed light on the putative DNA-bound state of full-length NsrR.	INTRO
+211	220	DNA-bound	protein_state	The expression of the genes of this operon is induced by a TCS consisting of the HK NsrK and the RR NsrR. Based on the crystal structures of both the domains, modeling was employed to shed light on the putative DNA-bound state of full-length NsrR.	INTRO
+230	241	full-length	protein_state	The expression of the genes of this operon is induced by a TCS consisting of the HK NsrK and the RR NsrR. Based on the crystal structures of both the domains, modeling was employed to shed light on the putative DNA-bound state of full-length NsrR.	INTRO
+242	246	NsrR	protein	The expression of the genes of this operon is induced by a TCS consisting of the HK NsrK and the RR NsrR. Based on the crystal structures of both the domains, modeling was employed to shed light on the putative DNA-bound state of full-length NsrR.	INTRO
+0	4	NsrR	protein	NsrR was expressed and purified as described, resulting in a homogenous protein as observed by size exclusion chromatography (Fig 1A), with a yield of 2 mg per liter of cell culture.	RESULTS
+9	31	expressed and purified	experimental_method	NsrR was expressed and purified as described, resulting in a homogenous protein as observed by size exclusion chromatography (Fig 1A), with a yield of 2 mg per liter of cell culture.	RESULTS
+95	124	size exclusion chromatography	experimental_method	NsrR was expressed and purified as described, resulting in a homogenous protein as observed by size exclusion chromatography (Fig 1A), with a yield of 2 mg per liter of cell culture.	RESULTS
+70	74	NsrR	protein	By calibrating the column with proteins of known molecular weight the NsrR full length protein elutes as a dimer.	RESULTS
+75	86	full length	protein_state	By calibrating the column with proteins of known molecular weight the NsrR full length protein elutes as a dimer.	RESULTS
+107	112	dimer	oligomeric_state	By calibrating the column with proteins of known molecular weight the NsrR full length protein elutes as a dimer.	RESULTS
+13	17	NsrR	protein	The purified NsrR protein has a theoretical molecular mass of 27.7 kDa and was >98% pure as assessed by SDS-PAGE (Fig 1B, indicated by *).	RESULTS
+44	58	molecular mass	evidence	The purified NsrR protein has a theoretical molecular mass of 27.7 kDa and was >98% pure as assessed by SDS-PAGE (Fig 1B, indicated by *).	RESULTS
+104	112	SDS-PAGE	experimental_method	The purified NsrR protein has a theoretical molecular mass of 27.7 kDa and was >98% pure as assessed by SDS-PAGE (Fig 1B, indicated by *).	RESULTS
+24	28	NsrR	protein	Surprisingly, over time NsrR degraded into two distinct fragments as visible on SDS-PAGE analysis using the same purified protein sample after one week (Fig 1C, indicated by ** and ***, respectively).	RESULTS
+80	88	SDS-PAGE	experimental_method	Surprisingly, over time NsrR degraded into two distinct fragments as visible on SDS-PAGE analysis using the same purified protein sample after one week (Fig 1C, indicated by ** and ***, respectively).	RESULTS
+26	55	size exclusion chromatography	experimental_method	This was also observed by size exclusion chromatography where a peak at an elution time of 18 min appeared (Fig 1A).	RESULTS
+29	55	mass spectrometry analysis	experimental_method	Both bands were subjected to mass spectrometry analysis.	RESULTS
+78	93	receiver domain	structure_element	The analysis revealed that the larger fragment (**) represents the N-terminal receiver domain (residues 1–119; referred to as NsrR-RD) whereas the smaller fragment (***) contained the C-terminal DNA-binding effector domain of NsrR (residues 129–243 including 21 amino acids derived from the expression tag; referred to as NsrR-ED) (Fig 1C).	RESULTS
+104	109	1–119	residue_range	The analysis revealed that the larger fragment (**) represents the N-terminal receiver domain (residues 1–119; referred to as NsrR-RD) whereas the smaller fragment (***) contained the C-terminal DNA-binding effector domain of NsrR (residues 129–243 including 21 amino acids derived from the expression tag; referred to as NsrR-ED) (Fig 1C).	RESULTS
+126	130	NsrR	protein	The analysis revealed that the larger fragment (**) represents the N-terminal receiver domain (residues 1–119; referred to as NsrR-RD) whereas the smaller fragment (***) contained the C-terminal DNA-binding effector domain of NsrR (residues 129–243 including 21 amino acids derived from the expression tag; referred to as NsrR-ED) (Fig 1C).	RESULTS
+131	133	RD	structure_element	The analysis revealed that the larger fragment (**) represents the N-terminal receiver domain (residues 1–119; referred to as NsrR-RD) whereas the smaller fragment (***) contained the C-terminal DNA-binding effector domain of NsrR (residues 129–243 including 21 amino acids derived from the expression tag; referred to as NsrR-ED) (Fig 1C).	RESULTS
+195	222	DNA-binding effector domain	structure_element	The analysis revealed that the larger fragment (**) represents the N-terminal receiver domain (residues 1–119; referred to as NsrR-RD) whereas the smaller fragment (***) contained the C-terminal DNA-binding effector domain of NsrR (residues 129–243 including 21 amino acids derived from the expression tag; referred to as NsrR-ED) (Fig 1C).	RESULTS
+226	230	NsrR	protein	The analysis revealed that the larger fragment (**) represents the N-terminal receiver domain (residues 1–119; referred to as NsrR-RD) whereas the smaller fragment (***) contained the C-terminal DNA-binding effector domain of NsrR (residues 129–243 including 21 amino acids derived from the expression tag; referred to as NsrR-ED) (Fig 1C).	RESULTS
+241	248	129–243	residue_range	The analysis revealed that the larger fragment (**) represents the N-terminal receiver domain (residues 1–119; referred to as NsrR-RD) whereas the smaller fragment (***) contained the C-terminal DNA-binding effector domain of NsrR (residues 129–243 including 21 amino acids derived from the expression tag; referred to as NsrR-ED) (Fig 1C).	RESULTS
+322	326	NsrR	protein	The analysis revealed that the larger fragment (**) represents the N-terminal receiver domain (residues 1–119; referred to as NsrR-RD) whereas the smaller fragment (***) contained the C-terminal DNA-binding effector domain of NsrR (residues 129–243 including 21 amino acids derived from the expression tag; referred to as NsrR-ED) (Fig 1C).	RESULTS
+327	329	ED	structure_element	The analysis revealed that the larger fragment (**) represents the N-terminal receiver domain (residues 1–119; referred to as NsrR-RD) whereas the smaller fragment (***) contained the C-terminal DNA-binding effector domain of NsrR (residues 129–243 including 21 amino acids derived from the expression tag; referred to as NsrR-ED) (Fig 1C).	RESULTS
+9	16	120–128	residue_range	Residues 120–128 form the linker connecting the RD and ED.	RESULTS
+26	32	linker	structure_element	Residues 120–128 form the linker connecting the RD and ED.	RESULTS
+48	50	RD	structure_element	Residues 120–128 form the linker connecting the RD and ED.	RESULTS
+55	57	ED	structure_element	Residues 120–128 form the linker connecting the RD and ED.	RESULTS
+23	34	full-length	protein_state	Such a cleavage of the full-length RR into two specific domains is not unusual and has been previously reported for other RRs as well.	RESULTS
+35	37	RR	protein_type	Such a cleavage of the full-length RR into two specific domains is not unusual and has been previously reported for other RRs as well.	RESULTS
+122	125	RRs	protein_type	Such a cleavage of the full-length RR into two specific domains is not unusual and has been previously reported for other RRs as well.	RESULTS
+0	26	Mass spectrometry analysis	experimental_method	Mass spectrometry analysis did not reveal the presence of any specific protease in the purified NsrR sample.	RESULTS
+96	100	NsrR	protein	Mass spectrometry analysis did not reveal the presence of any specific protease in the purified NsrR sample.	RESULTS
+55	59	PMSF	chemical	Furthermore, addition of a protease inhibitor, such as PMSF (Phenylmethylsulfonyl fluoride) and AEBSF {4-(2-Aminoethyl) benzenesulfonyl fluoride hydrochloride}, even at high concentrations, did not inhibit proteolysis (data not shown).	RESULTS
+61	90	Phenylmethylsulfonyl fluoride	chemical	Furthermore, addition of a protease inhibitor, such as PMSF (Phenylmethylsulfonyl fluoride) and AEBSF {4-(2-Aminoethyl) benzenesulfonyl fluoride hydrochloride}, even at high concentrations, did not inhibit proteolysis (data not shown).	RESULTS
+96	101	AEBSF	chemical	Furthermore, addition of a protease inhibitor, such as PMSF (Phenylmethylsulfonyl fluoride) and AEBSF {4-(2-Aminoethyl) benzenesulfonyl fluoride hydrochloride}, even at high concentrations, did not inhibit proteolysis (data not shown).	RESULTS
+103	158	4-(2-Aminoethyl) benzenesulfonyl fluoride hydrochloride	chemical	Furthermore, addition of a protease inhibitor, such as PMSF (Phenylmethylsulfonyl fluoride) and AEBSF {4-(2-Aminoethyl) benzenesulfonyl fluoride hydrochloride}, even at high concentrations, did not inhibit proteolysis (data not shown).	RESULTS
+0	12	Purification	experimental_method	Purification of NsrR and SDS PAGE analysis of purified NsrR directly and one week after purification.	FIG
+16	20	NsrR	protein	Purification of NsrR and SDS PAGE analysis of purified NsrR directly and one week after purification.	FIG
+25	33	SDS PAGE	experimental_method	Purification of NsrR and SDS PAGE analysis of purified NsrR directly and one week after purification.	FIG
+55	59	NsrR	protein	Purification of NsrR and SDS PAGE analysis of purified NsrR directly and one week after purification.	FIG
+4	19	Elution profile	evidence	(a) Elution profile of size-exclusion chromatography step of NsrR. The y-axis represents the UV absorption of the protein at 280 nm, while the x-axis represents the elution volume.	FIG
+23	52	size-exclusion chromatography	experimental_method	(a) Elution profile of size-exclusion chromatography step of NsrR. The y-axis represents the UV absorption of the protein at 280 nm, while the x-axis represents the elution volume.	FIG
+61	65	NsrR	protein	(a) Elution profile of size-exclusion chromatography step of NsrR. The y-axis represents the UV absorption of the protein at 280 nm, while the x-axis represents the elution volume.	FIG
+29	41	chromatogram	evidence	The bold line represents the chromatogram of freshly purified NsrR while the dashed line shows the chromatogram of the same NsrR protein after one week.	FIG
+62	66	NsrR	protein	The bold line represents the chromatogram of freshly purified NsrR while the dashed line shows the chromatogram of the same NsrR protein after one week.	FIG
+99	111	chromatogram	evidence	The bold line represents the chromatogram of freshly purified NsrR while the dashed line shows the chromatogram of the same NsrR protein after one week.	FIG
+124	128	NsrR	protein	The bold line represents the chromatogram of freshly purified NsrR while the dashed line shows the chromatogram of the same NsrR protein after one week.	FIG
+21	25	NsrR	protein	(b) Freshly purified NsrR protein, and (c) NsrR protein after one week.	FIG
+43	47	NsrR	protein	(b) Freshly purified NsrR protein, and (c) NsrR protein after one week.	FIG
+56	60	NsrR	protein	Lanes: M represents the PAGE Ruler Unstained Ladder; 1: NsrR after a two-step purification; 2: NsrR one week after purification.	FIG
+95	99	NsrR	protein	Lanes: M represents the PAGE Ruler Unstained Ladder; 1: NsrR after a two-step purification; 2: NsrR one week after purification.	FIG
+17	28	full-length	protein_state	* corresponds to full-length NsrR protein at 27 kDa, while ** and *** correspond to the NsrR-RD and NsrR-ED domain at around 13 kDa, respectively.	FIG
+29	33	NsrR	protein	* corresponds to full-length NsrR protein at 27 kDa, while ** and *** correspond to the NsrR-RD and NsrR-ED domain at around 13 kDa, respectively.	FIG
+88	92	NsrR	protein	* corresponds to full-length NsrR protein at 27 kDa, while ** and *** correspond to the NsrR-RD and NsrR-ED domain at around 13 kDa, respectively.	FIG
+93	95	RD	structure_element	* corresponds to full-length NsrR protein at 27 kDa, while ** and *** correspond to the NsrR-RD and NsrR-ED domain at around 13 kDa, respectively.	FIG
+100	104	NsrR	protein	* corresponds to full-length NsrR protein at 27 kDa, while ** and *** correspond to the NsrR-RD and NsrR-ED domain at around 13 kDa, respectively.	FIG
+105	107	ED	structure_element	* corresponds to full-length NsrR protein at 27 kDa, while ** and *** correspond to the NsrR-RD and NsrR-ED domain at around 13 kDa, respectively.	FIG
+23	31	crystals	evidence	Since formation of the crystals took around one month, it is not surprising that this cleavage also occurred in the crystallization drop.	RESULTS
+0	4	NsrR	protein	NsrR was crystallized yielding two crystal forms, which were distinguishable by visual inspection.	RESULTS
+9	21	crystallized	experimental_method	NsrR was crystallized yielding two crystal forms, which were distinguishable by visual inspection.	RESULTS
+33	42	structure	evidence	Initially, we tried to solve the structure of NsrR by molecular replacement, which was not successful.	RESULTS
+46	50	NsrR	protein	Initially, we tried to solve the structure of NsrR by molecular replacement, which was not successful.	RESULTS
+54	75	molecular replacement	experimental_method	Initially, we tried to solve the structure of NsrR by molecular replacement, which was not successful.	RESULTS
+20	38	heavy atom phasing	experimental_method	Therefore, we tried heavy atom phasing using a platinum compound.	RESULTS
+47	55	platinum	chemical	Therefore, we tried heavy atom phasing using a platinum compound.	RESULTS
+48	56	crystals	evidence	This succeeded for the rectangular plate-shaped crystals.	RESULTS
+10	19	structure	evidence	After the structure was solved, it became evident that these crystals contained two monomers of the ED of NsrR in the asymmetric unit.	RESULTS
+61	69	crystals	evidence	After the structure was solved, it became evident that these crystals contained two monomers of the ED of NsrR in the asymmetric unit.	RESULTS
+84	92	monomers	oligomeric_state	After the structure was solved, it became evident that these crystals contained two monomers of the ED of NsrR in the asymmetric unit.	RESULTS
+100	102	ED	structure_element	After the structure was solved, it became evident that these crystals contained two monomers of the ED of NsrR in the asymmetric unit.	RESULTS
+106	110	NsrR	protein	After the structure was solved, it became evident that these crystals contained two monomers of the ED of NsrR in the asymmetric unit.	RESULTS
+27	36	structure	evidence	We also tried to solve the structure of the thin plate-shaped crystals with this template, but the resulting model generated was not sufficient.	RESULTS
+62	70	crystals	evidence	We also tried to solve the structure of the thin plate-shaped crystals with this template, but the resulting model generated was not sufficient.	RESULTS
+33	41	crystals	evidence	Therefore, we thought that these crystals contained the N-terminal domain of NsrR and successfully phased this dataset using molecular replacement with the N-terminal domain of PhoB (PDB code: 1B00; as a template.	RESULTS
+56	73	N-terminal domain	structure_element	Therefore, we thought that these crystals contained the N-terminal domain of NsrR and successfully phased this dataset using molecular replacement with the N-terminal domain of PhoB (PDB code: 1B00; as a template.	RESULTS
+77	81	NsrR	protein	Therefore, we thought that these crystals contained the N-terminal domain of NsrR and successfully phased this dataset using molecular replacement with the N-terminal domain of PhoB (PDB code: 1B00; as a template.	RESULTS
+125	146	molecular replacement	experimental_method	Therefore, we thought that these crystals contained the N-terminal domain of NsrR and successfully phased this dataset using molecular replacement with the N-terminal domain of PhoB (PDB code: 1B00; as a template.	RESULTS
+156	173	N-terminal domain	structure_element	Therefore, we thought that these crystals contained the N-terminal domain of NsrR and successfully phased this dataset using molecular replacement with the N-terminal domain of PhoB (PDB code: 1B00; as a template.	RESULTS
+177	181	PhoB	protein	Therefore, we thought that these crystals contained the N-terminal domain of NsrR and successfully phased this dataset using molecular replacement with the N-terminal domain of PhoB (PDB code: 1B00; as a template.	RESULTS
+67	75	monomers	oligomeric_state	This approach revealed that this crystal form indeed contained two monomers of the RD of NsrR in the asymmetric unit.	RESULTS
+83	85	RD	structure_element	This approach revealed that this crystal form indeed contained two monomers of the RD of NsrR in the asymmetric unit.	RESULTS
+89	93	NsrR	protein	This approach revealed that this crystal form indeed contained two monomers of the RD of NsrR in the asymmetric unit.	RESULTS
+108	116	crystals	evidence	Since both crystals forms were obtained in the same drop it is not surprising that, when dissolving several crystals and performing subsequent mass-spectrometry to identify the protein in the crystals, it yielded peptide fragments throughout the NsrR sequence.	RESULTS
+143	160	mass-spectrometry	experimental_method	Since both crystals forms were obtained in the same drop it is not surprising that, when dissolving several crystals and performing subsequent mass-spectrometry to identify the protein in the crystals, it yielded peptide fragments throughout the NsrR sequence.	RESULTS
+192	200	crystals	evidence	Since both crystals forms were obtained in the same drop it is not surprising that, when dissolving several crystals and performing subsequent mass-spectrometry to identify the protein in the crystals, it yielded peptide fragments throughout the NsrR sequence.	RESULTS
+246	250	NsrR	protein	Since both crystals forms were obtained in the same drop it is not surprising that, when dissolving several crystals and performing subsequent mass-spectrometry to identify the protein in the crystals, it yielded peptide fragments throughout the NsrR sequence.	RESULTS
+20	33	crystal forms	evidence	In summary, the two crystal forms contained one of the two domains, respectively, such that both domains were successfully crystallized.	RESULTS
+123	135	crystallized	experimental_method	In summary, the two crystal forms contained one of the two domains, respectively, such that both domains were successfully crystallized.	RESULTS
+18	36	crystal structures	evidence	We determined the crystal structures of NsrR-RD and NsrR-ED separately.	RESULTS
+40	44	NsrR	protein	We determined the crystal structures of NsrR-RD and NsrR-ED separately.	RESULTS
+45	47	RD	structure_element	We determined the crystal structures of NsrR-RD and NsrR-ED separately.	RESULTS
+52	56	NsrR	protein	We determined the crystal structures of NsrR-RD and NsrR-ED separately.	RESULTS
+57	59	ED	structure_element	We determined the crystal structures of NsrR-RD and NsrR-ED separately.	RESULTS
+23	36	linker region	structure_element	However, a part of the linker region (residues 120–128; 120RRSQQFIQQ128; underlined are the amino acid residues not visible in either domain) could not be traced in the electron density.	RESULTS
+47	54	120–128	residue_range	However, a part of the linker region (residues 120–128; 120RRSQQFIQQ128; underlined are the amino acid residues not visible in either domain) could not be traced in the electron density.	RESULTS
+56	71	120RRSQQFIQQ128	structure_element	However, a part of the linker region (residues 120–128; 120RRSQQFIQQ128; underlined are the amino acid residues not visible in either domain) could not be traced in the electron density.	RESULTS
+169	185	electron density	evidence	However, a part of the linker region (residues 120–128; 120RRSQQFIQQ128; underlined are the amino acid residues not visible in either domain) could not be traced in the electron density.	RESULTS
+8	17	structure	evidence	Overall structure of the N-terminal NsrR receiver domain (NsrR-RD)	RESULTS
+36	40	NsrR	protein	Overall structure of the N-terminal NsrR receiver domain (NsrR-RD)	RESULTS
+41	56	receiver domain	structure_element	Overall structure of the N-terminal NsrR receiver domain (NsrR-RD)	RESULTS
+58	62	NsrR	protein	Overall structure of the N-terminal NsrR receiver domain (NsrR-RD)	RESULTS
+63	65	RD	structure_element	Overall structure of the N-terminal NsrR receiver domain (NsrR-RD)	RESULTS
+4	13	structure	evidence	The structure of the NsrR-RD was determined at a resolution of 1.8 Å (Table 1).	RESULTS
+21	25	NsrR	protein	The structure of the NsrR-RD was determined at a resolution of 1.8 Å (Table 1).	RESULTS
+26	28	RD	structure_element	The structure of the NsrR-RD was determined at a resolution of 1.8 Å (Table 1).	RESULTS
+4	9	Rwork	evidence	The Rwork and Rfree values after refinement were 0.17 and 0.22, respectively.	RESULTS
+14	19	Rfree	evidence	The Rwork and Rfree values after refinement were 0.17 and 0.22, respectively.	RESULTS
+0	23	Ramachandran validation	evidence	Ramachandran validation revealed that all residues (100%, 236 amino acids) were in the preferred or allowed regions.	RESULTS
+4	13	structure	evidence	The structure contained many ethylene glycol molecules arising from the cryo-protecting procedure.	RESULTS
+29	44	ethylene glycol	chemical	The structure contained many ethylene glycol molecules arising from the cryo-protecting procedure.	RESULTS
+43	47	NsrR	protein	The asymmetric unit contains two copies of NsrR-RD.	RESULTS
+48	50	RD	structure_element	The asymmetric unit contains two copies of NsrR-RD.	RESULTS
+31	46	receiver domain	structure_element	Although the entire N-terminal receiver domain is composed of residues Met1-Leu119, only residues Asn4 to Arg121 of chain A (including residues Arg120 and Arg121 of the linker) and Gln5 to Ser122 of chain B (including residues Arg120 until Ser122 of the linker) could be traced in the electron density of NsrR-RD.	RESULTS
+71	82	Met1-Leu119	residue_range	Although the entire N-terminal receiver domain is composed of residues Met1-Leu119, only residues Asn4 to Arg121 of chain A (including residues Arg120 and Arg121 of the linker) and Gln5 to Ser122 of chain B (including residues Arg120 until Ser122 of the linker) could be traced in the electron density of NsrR-RD.	RESULTS
+98	112	Asn4 to Arg121	residue_range	Although the entire N-terminal receiver domain is composed of residues Met1-Leu119, only residues Asn4 to Arg121 of chain A (including residues Arg120 and Arg121 of the linker) and Gln5 to Ser122 of chain B (including residues Arg120 until Ser122 of the linker) could be traced in the electron density of NsrR-RD.	RESULTS
+116	123	chain A	structure_element	Although the entire N-terminal receiver domain is composed of residues Met1-Leu119, only residues Asn4 to Arg121 of chain A (including residues Arg120 and Arg121 of the linker) and Gln5 to Ser122 of chain B (including residues Arg120 until Ser122 of the linker) could be traced in the electron density of NsrR-RD.	RESULTS
+144	150	Arg120	residue_name_number	Although the entire N-terminal receiver domain is composed of residues Met1-Leu119, only residues Asn4 to Arg121 of chain A (including residues Arg120 and Arg121 of the linker) and Gln5 to Ser122 of chain B (including residues Arg120 until Ser122 of the linker) could be traced in the electron density of NsrR-RD.	RESULTS
+155	161	Arg121	residue_name_number	Although the entire N-terminal receiver domain is composed of residues Met1-Leu119, only residues Asn4 to Arg121 of chain A (including residues Arg120 and Arg121 of the linker) and Gln5 to Ser122 of chain B (including residues Arg120 until Ser122 of the linker) could be traced in the electron density of NsrR-RD.	RESULTS
+169	175	linker	structure_element	Although the entire N-terminal receiver domain is composed of residues Met1-Leu119, only residues Asn4 to Arg121 of chain A (including residues Arg120 and Arg121 of the linker) and Gln5 to Ser122 of chain B (including residues Arg120 until Ser122 of the linker) could be traced in the electron density of NsrR-RD.	RESULTS
+181	195	Gln5 to Ser122	residue_range	Although the entire N-terminal receiver domain is composed of residues Met1-Leu119, only residues Asn4 to Arg121 of chain A (including residues Arg120 and Arg121 of the linker) and Gln5 to Ser122 of chain B (including residues Arg120 until Ser122 of the linker) could be traced in the electron density of NsrR-RD.	RESULTS
+199	206	chain B	structure_element	Although the entire N-terminal receiver domain is composed of residues Met1-Leu119, only residues Asn4 to Arg121 of chain A (including residues Arg120 and Arg121 of the linker) and Gln5 to Ser122 of chain B (including residues Arg120 until Ser122 of the linker) could be traced in the electron density of NsrR-RD.	RESULTS
+227	246	Arg120 until Ser122	residue_range	Although the entire N-terminal receiver domain is composed of residues Met1-Leu119, only residues Asn4 to Arg121 of chain A (including residues Arg120 and Arg121 of the linker) and Gln5 to Ser122 of chain B (including residues Arg120 until Ser122 of the linker) could be traced in the electron density of NsrR-RD.	RESULTS
+254	260	linker	structure_element	Although the entire N-terminal receiver domain is composed of residues Met1-Leu119, only residues Asn4 to Arg121 of chain A (including residues Arg120 and Arg121 of the linker) and Gln5 to Ser122 of chain B (including residues Arg120 until Ser122 of the linker) could be traced in the electron density of NsrR-RD.	RESULTS
+285	301	electron density	evidence	Although the entire N-terminal receiver domain is composed of residues Met1-Leu119, only residues Asn4 to Arg121 of chain A (including residues Arg120 and Arg121 of the linker) and Gln5 to Ser122 of chain B (including residues Arg120 until Ser122 of the linker) could be traced in the electron density of NsrR-RD.	RESULTS
+305	309	NsrR	protein	Although the entire N-terminal receiver domain is composed of residues Met1-Leu119, only residues Asn4 to Arg121 of chain A (including residues Arg120 and Arg121 of the linker) and Gln5 to Ser122 of chain B (including residues Arg120 until Ser122 of the linker) could be traced in the electron density of NsrR-RD.	RESULTS
+310	312	RD	structure_element	Although the entire N-terminal receiver domain is composed of residues Met1-Leu119, only residues Asn4 to Arg121 of chain A (including residues Arg120 and Arg121 of the linker) and Gln5 to Ser122 of chain B (including residues Arg120 until Ser122 of the linker) could be traced in the electron density of NsrR-RD.	RESULTS
+4	9	Asn85	residue_name_number	For Asn85, Asp86, and Glu87 of chain A, poor electron density was observed for the side chains and, thus, these side chains were deleted during refinement and are not present in the final structure.	RESULTS
+11	16	Asp86	residue_name_number	For Asn85, Asp86, and Glu87 of chain A, poor electron density was observed for the side chains and, thus, these side chains were deleted during refinement and are not present in the final structure.	RESULTS
+22	27	Glu87	residue_name_number	For Asn85, Asp86, and Glu87 of chain A, poor electron density was observed for the side chains and, thus, these side chains were deleted during refinement and are not present in the final structure.	RESULTS
+31	38	chain A	structure_element	For Asn85, Asp86, and Glu87 of chain A, poor electron density was observed for the side chains and, thus, these side chains were deleted during refinement and are not present in the final structure.	RESULTS
+45	61	electron density	evidence	For Asn85, Asp86, and Glu87 of chain A, poor electron density was observed for the side chains and, thus, these side chains were deleted during refinement and are not present in the final structure.	RESULTS
+188	197	structure	evidence	For Asn85, Asp86, and Glu87 of chain A, poor electron density was observed for the side chains and, thus, these side chains were deleted during refinement and are not present in the final structure.	RESULTS
+14	22	monomers	oligomeric_state	Since the two monomers of NsrR-RD were virtually identical (rmsd of 0.6 Å over 116 Cα atoms for the two monomers).	RESULTS
+26	30	NsrR	protein	Since the two monomers of NsrR-RD were virtually identical (rmsd of 0.6 Å over 116 Cα atoms for the two monomers).	RESULTS
+31	33	RD	structure_element	Since the two monomers of NsrR-RD were virtually identical (rmsd of 0.6 Å over 116 Cα atoms for the two monomers).	RESULTS
+60	64	rmsd	evidence	Since the two monomers of NsrR-RD were virtually identical (rmsd of 0.6 Å over 116 Cα atoms for the two monomers).	RESULTS
+104	112	monomers	oligomeric_state	Since the two monomers of NsrR-RD were virtually identical (rmsd of 0.6 Å over 116 Cα atoms for the two monomers).	RESULTS
+23	32	structure	evidence	Therefore, the overall structure is described for monomer A only.	RESULTS
+50	57	monomer	oligomeric_state	Therefore, the overall structure is described for monomer A only.	RESULTS
+58	59	A	structure_element	Therefore, the overall structure is described for monomer A only.	RESULTS
+0	4	NsrR	protein	NsrR-RD structurally adopts a αβ doubly-wound fold previously observed in OmpR/PhoB type regulators.	RESULTS
+5	7	RD	structure_element	NsrR-RD structurally adopts a αβ doubly-wound fold previously observed in OmpR/PhoB type regulators.	RESULTS
+30	50	αβ doubly-wound fold	structure_element	NsrR-RD structurally adopts a αβ doubly-wound fold previously observed in OmpR/PhoB type regulators.	RESULTS
+74	99	OmpR/PhoB type regulators	protein_type	NsrR-RD structurally adopts a αβ doubly-wound fold previously observed in OmpR/PhoB type regulators.	RESULTS
+5	14	β-strands	structure_element	Five β-strands (β1-β5) are arranged in a parallel fashion constituting the central core of the structure, which is surrounded by two α-helices (α1 and α5) on one and three helices (α2, α3, α4) on the other side (Fig 2).	RESULTS
+16	21	β1-β5	structure_element	Five β-strands (β1-β5) are arranged in a parallel fashion constituting the central core of the structure, which is surrounded by two α-helices (α1 and α5) on one and three helices (α2, α3, α4) on the other side (Fig 2).	RESULTS
+95	104	structure	evidence	Five β-strands (β1-β5) are arranged in a parallel fashion constituting the central core of the structure, which is surrounded by two α-helices (α1 and α5) on one and three helices (α2, α3, α4) on the other side (Fig 2).	RESULTS
+133	142	α-helices	structure_element	Five β-strands (β1-β5) are arranged in a parallel fashion constituting the central core of the structure, which is surrounded by two α-helices (α1 and α5) on one and three helices (α2, α3, α4) on the other side (Fig 2).	RESULTS
+144	146	α1	structure_element	Five β-strands (β1-β5) are arranged in a parallel fashion constituting the central core of the structure, which is surrounded by two α-helices (α1 and α5) on one and three helices (α2, α3, α4) on the other side (Fig 2).	RESULTS
+151	153	α5	structure_element	Five β-strands (β1-β5) are arranged in a parallel fashion constituting the central core of the structure, which is surrounded by two α-helices (α1 and α5) on one and three helices (α2, α3, α4) on the other side (Fig 2).	RESULTS
+172	179	helices	structure_element	Five β-strands (β1-β5) are arranged in a parallel fashion constituting the central core of the structure, which is surrounded by two α-helices (α1 and α5) on one and three helices (α2, α3, α4) on the other side (Fig 2).	RESULTS
+181	183	α2	structure_element	Five β-strands (β1-β5) are arranged in a parallel fashion constituting the central core of the structure, which is surrounded by two α-helices (α1 and α5) on one and three helices (α2, α3, α4) on the other side (Fig 2).	RESULTS
+185	187	α3	structure_element	Five β-strands (β1-β5) are arranged in a parallel fashion constituting the central core of the structure, which is surrounded by two α-helices (α1 and α5) on one and three helices (α2, α3, α4) on the other side (Fig 2).	RESULTS
+189	191	α4	structure_element	Five β-strands (β1-β5) are arranged in a parallel fashion constituting the central core of the structure, which is surrounded by two α-helices (α1 and α5) on one and three helices (α2, α3, α4) on the other side (Fig 2).	RESULTS
+4	8	NsrR	protein	The NsrR-RD structure shows a β1-α1-β2-α2-β3-α3-β4-α4-β5-α5 topology as also observed for other RRs.	RESULTS
+9	11	RD	structure_element	The NsrR-RD structure shows a β1-α1-β2-α2-β3-α3-β4-α4-β5-α5 topology as also observed for other RRs.	RESULTS
+12	21	structure	evidence	The NsrR-RD structure shows a β1-α1-β2-α2-β3-α3-β4-α4-β5-α5 topology as also observed for other RRs.	RESULTS
+30	59	β1-α1-β2-α2-β3-α3-β4-α4-β5-α5	structure_element	The NsrR-RD structure shows a β1-α1-β2-α2-β3-α3-β4-α4-β5-α5 topology as also observed for other RRs.	RESULTS
+96	99	RRs	protein_type	The NsrR-RD structure shows a β1-α1-β2-α2-β3-α3-β4-α4-β5-α5 topology as also observed for other RRs.	RESULTS
+0	9	Structure	evidence	Structure of NsrR-RD.	FIG
+13	17	NsrR	protein	Structure of NsrR-RD.	FIG
+18	20	RD	structure_element	Structure of NsrR-RD.	FIG
+30	37	helices	structure_element	Cartoon representation of the helices (α1 – α5) and β-sheets (β1 - β5).	FIG
+39	46	α1 – α5	structure_element	Cartoon representation of the helices (α1 – α5) and β-sheets (β1 - β5).	FIG
+52	60	β-sheets	structure_element	Cartoon representation of the helices (α1 – α5) and β-sheets (β1 - β5).	FIG
+62	69	β1 - β5	structure_element	Cartoon representation of the helices (α1 – α5) and β-sheets (β1 - β5).	FIG
+52	68	receiver domains	structure_element	Structural areas with the highest variations to the receiver domains of DrrB (pink, 1P2F), MtrA (grey, 2GWR), and PhoB (blue, 1B00) are marked in separate boxes.	FIG
+72	76	DrrB	protein	Structural areas with the highest variations to the receiver domains of DrrB (pink, 1P2F), MtrA (grey, 2GWR), and PhoB (blue, 1B00) are marked in separate boxes.	FIG
+91	95	MtrA	protein	Structural areas with the highest variations to the receiver domains of DrrB (pink, 1P2F), MtrA (grey, 2GWR), and PhoB (blue, 1B00) are marked in separate boxes.	FIG
+114	118	PhoB	protein	Structural areas with the highest variations to the receiver domains of DrrB (pink, 1P2F), MtrA (grey, 2GWR), and PhoB (blue, 1B00) are marked in separate boxes.	FIG
+0	10	Comparison	experimental_method	Comparison with structures of other receiver domains	RESULTS
+16	26	structures	evidence	Comparison with structures of other receiver domains	RESULTS
+36	52	receiver domains	structure_element	Comparison with structures of other receiver domains	RESULTS
+0	4	NsrR	protein	NsrR belongs to the OmpR/PhoB family of RRs.	RESULTS
+20	36	OmpR/PhoB family	protein_type	NsrR belongs to the OmpR/PhoB family of RRs.	RESULTS
+40	43	RRs	protein_type	NsrR belongs to the OmpR/PhoB family of RRs.	RESULTS
+4	19	receiver domain	structure_element	The receiver domain of NsrR was superimposed with other structurally characterized receiver domains from the OmpR/PhoB family, such as DrrB, KdpE, MtrA, and the crystal structure of only the receiver domain of PhoB. The rmsd of the overlays and the corresponding PDB codes used are highlighted in Table 2.	RESULTS
+23	27	NsrR	protein	The receiver domain of NsrR was superimposed with other structurally characterized receiver domains from the OmpR/PhoB family, such as DrrB, KdpE, MtrA, and the crystal structure of only the receiver domain of PhoB. The rmsd of the overlays and the corresponding PDB codes used are highlighted in Table 2.	RESULTS
+32	44	superimposed	experimental_method	The receiver domain of NsrR was superimposed with other structurally characterized receiver domains from the OmpR/PhoB family, such as DrrB, KdpE, MtrA, and the crystal structure of only the receiver domain of PhoB. The rmsd of the overlays and the corresponding PDB codes used are highlighted in Table 2.	RESULTS
+83	99	receiver domains	structure_element	The receiver domain of NsrR was superimposed with other structurally characterized receiver domains from the OmpR/PhoB family, such as DrrB, KdpE, MtrA, and the crystal structure of only the receiver domain of PhoB. The rmsd of the overlays and the corresponding PDB codes used are highlighted in Table 2.	RESULTS
+109	125	OmpR/PhoB family	protein_type	The receiver domain of NsrR was superimposed with other structurally characterized receiver domains from the OmpR/PhoB family, such as DrrB, KdpE, MtrA, and the crystal structure of only the receiver domain of PhoB. The rmsd of the overlays and the corresponding PDB codes used are highlighted in Table 2.	RESULTS
+135	139	DrrB	protein	The receiver domain of NsrR was superimposed with other structurally characterized receiver domains from the OmpR/PhoB family, such as DrrB, KdpE, MtrA, and the crystal structure of only the receiver domain of PhoB. The rmsd of the overlays and the corresponding PDB codes used are highlighted in Table 2.	RESULTS
+141	145	KdpE	protein	The receiver domain of NsrR was superimposed with other structurally characterized receiver domains from the OmpR/PhoB family, such as DrrB, KdpE, MtrA, and the crystal structure of only the receiver domain of PhoB. The rmsd of the overlays and the corresponding PDB codes used are highlighted in Table 2.	RESULTS
+147	151	MtrA	protein	The receiver domain of NsrR was superimposed with other structurally characterized receiver domains from the OmpR/PhoB family, such as DrrB, KdpE, MtrA, and the crystal structure of only the receiver domain of PhoB. The rmsd of the overlays and the corresponding PDB codes used are highlighted in Table 2.	RESULTS
+161	178	crystal structure	evidence	The receiver domain of NsrR was superimposed with other structurally characterized receiver domains from the OmpR/PhoB family, such as DrrB, KdpE, MtrA, and the crystal structure of only the receiver domain of PhoB. The rmsd of the overlays and the corresponding PDB codes used are highlighted in Table 2.	RESULTS
+191	206	receiver domain	structure_element	The receiver domain of NsrR was superimposed with other structurally characterized receiver domains from the OmpR/PhoB family, such as DrrB, KdpE, MtrA, and the crystal structure of only the receiver domain of PhoB. The rmsd of the overlays and the corresponding PDB codes used are highlighted in Table 2.	RESULTS
+210	214	PhoB	protein	The receiver domain of NsrR was superimposed with other structurally characterized receiver domains from the OmpR/PhoB family, such as DrrB, KdpE, MtrA, and the crystal structure of only the receiver domain of PhoB. The rmsd of the overlays and the corresponding PDB codes used are highlighted in Table 2.	RESULTS
+220	224	rmsd	evidence	The receiver domain of NsrR was superimposed with other structurally characterized receiver domains from the OmpR/PhoB family, such as DrrB, KdpE, MtrA, and the crystal structure of only the receiver domain of PhoB. The rmsd of the overlays and the corresponding PDB codes used are highlighted in Table 2.	RESULTS
+232	240	overlays	experimental_method	The receiver domain of NsrR was superimposed with other structurally characterized receiver domains from the OmpR/PhoB family, such as DrrB, KdpE, MtrA, and the crystal structure of only the receiver domain of PhoB. The rmsd of the overlays and the corresponding PDB codes used are highlighted in Table 2.	RESULTS
+0	15	Superimposition	experimental_method	Superimposition of the structures revealed that helix α4 is slightly rotated outward in NsrR-RD (Fig 2).	RESULTS
+23	33	structures	evidence	Superimposition of the structures revealed that helix α4 is slightly rotated outward in NsrR-RD (Fig 2).	RESULTS
+48	53	helix	structure_element	Superimposition of the structures revealed that helix α4 is slightly rotated outward in NsrR-RD (Fig 2).	RESULTS
+54	56	α4	structure_element	Superimposition of the structures revealed that helix α4 is slightly rotated outward in NsrR-RD (Fig 2).	RESULTS
+88	92	NsrR	protein	Superimposition of the structures revealed that helix α4 is slightly rotated outward in NsrR-RD (Fig 2).	RESULTS
+93	95	RD	structure_element	Superimposition of the structures revealed that helix α4 is slightly rotated outward in NsrR-RD (Fig 2).	RESULTS
+3	19	receiver domains	structure_element	In receiver domains of response regulators, helix α4 has been shown to be a crucial part of the dimerization interface.	RESULTS
+23	42	response regulators	protein_type	In receiver domains of response regulators, helix α4 has been shown to be a crucial part of the dimerization interface.	RESULTS
+44	49	helix	structure_element	In receiver domains of response regulators, helix α4 has been shown to be a crucial part of the dimerization interface.	RESULTS
+50	52	α4	structure_element	In receiver domains of response regulators, helix α4 has been shown to be a crucial part of the dimerization interface.	RESULTS
+96	118	dimerization interface	site	In receiver domains of response regulators, helix α4 has been shown to be a crucial part of the dimerization interface.	RESULTS
+13	18	helix	structure_element	Furthermore, helix α4 in NsrR is shorter than in other RRs.	RESULTS
+19	21	α4	structure_element	Furthermore, helix α4 in NsrR is shorter than in other RRs.	RESULTS
+25	29	NsrR	protein	Furthermore, helix α4 in NsrR is shorter than in other RRs.	RESULTS
+55	58	RRs	protein_type	Furthermore, helix α4 in NsrR is shorter than in other RRs.	RESULTS
+4	22	first helical turn	structure_element	The first helical turn is unwound and adopts an unstructured region (see Fig 2).	RESULTS
+26	33	unwound	protein_state	The first helical turn is unwound and adopts an unstructured region (see Fig 2).	RESULTS
+48	60	unstructured	protein_state	The first helical turn is unwound and adopts an unstructured region (see Fig 2).	RESULTS
+44	49	helix	structure_element	A slightly outward rotation or unwinding of helix α4 has been observed in the structures of other RD of regulators.	RESULTS
+50	52	α4	structure_element	A slightly outward rotation or unwinding of helix α4 has been observed in the structures of other RD of regulators.	RESULTS
+78	88	structures	evidence	A slightly outward rotation or unwinding of helix α4 has been observed in the structures of other RD of regulators.	RESULTS
+98	100	RD	structure_element	A slightly outward rotation or unwinding of helix α4 has been observed in the structures of other RD of regulators.	RESULTS
+17	26	structure	evidence	For example, the structure of BaeR and RegX3 displayed a completely unwound helix α4.	RESULTS
+30	34	BaeR	protein	For example, the structure of BaeR and RegX3 displayed a completely unwound helix α4.	RESULTS
+39	44	RegX3	protein	For example, the structure of BaeR and RegX3 displayed a completely unwound helix α4.	RESULTS
+68	75	unwound	protein_state	For example, the structure of BaeR and RegX3 displayed a completely unwound helix α4.	RESULTS
+76	81	helix	structure_element	For example, the structure of BaeR and RegX3 displayed a completely unwound helix α4.	RESULTS
+82	84	α4	structure_element	For example, the structure of BaeR and RegX3 displayed a completely unwound helix α4.	RESULTS
+7	16	structure	evidence	In the structure of DrrD, helix α4 is only partially displaced.	RESULTS
+20	24	DrrD	protein	In the structure of DrrD, helix α4 is only partially displaced.	RESULTS
+26	31	helix	structure_element	In the structure of DrrD, helix α4 is only partially displaced.	RESULTS
+32	34	α4	structure_element	In the structure of DrrD, helix α4 is only partially displaced.	RESULTS
+7	22	receiver domain	structure_element	In the receiver domain of NsrR, helix α4 is also partially displaced but in a different direction (S1 Fig).	RESULTS
+26	30	NsrR	protein	In the receiver domain of NsrR, helix α4 is also partially displaced but in a different direction (S1 Fig).	RESULTS
+32	37	helix	structure_element	In the receiver domain of NsrR, helix α4 is also partially displaced but in a different direction (S1 Fig).	RESULTS
+38	40	α4	structure_element	In the receiver domain of NsrR, helix α4 is also partially displaced but in a different direction (S1 Fig).	RESULTS
+127	132	helix	structure_element	Inspection of the crystal contacts revealed no major interactions in this region that could have influenced the orientation of helix α4.	RESULTS
+133	135	α4	structure_element	Inspection of the crystal contacts revealed no major interactions in this region that could have influenced the orientation of helix α4.	RESULTS
+13	17	NsrR	protein	Furthermore, NsrR is crystallized as a monomer, and investigation of the symmetry-related molecules did not reveal a functional dimer within the crystal.	RESULTS
+21	33	crystallized	experimental_method	Furthermore, NsrR is crystallized as a monomer, and investigation of the symmetry-related molecules did not reveal a functional dimer within the crystal.	RESULTS
+39	46	monomer	oligomeric_state	Furthermore, NsrR is crystallized as a monomer, and investigation of the symmetry-related molecules did not reveal a functional dimer within the crystal.	RESULTS
+128	133	dimer	oligomeric_state	Furthermore, NsrR is crystallized as a monomer, and investigation of the symmetry-related molecules did not reveal a functional dimer within the crystal.	RESULTS
+145	152	crystal	evidence	Furthermore, NsrR is crystallized as a monomer, and investigation of the symmetry-related molecules did not reveal a functional dimer within the crystal.	RESULTS
+76	81	helix	structure_element	This could explain the flexibility and thereby the different orientation of helix α4 in NsrR.	RESULTS
+82	84	α4	structure_element	This could explain the flexibility and thereby the different orientation of helix α4 in NsrR.	RESULTS
+88	92	NsrR	protein	This could explain the flexibility and thereby the different orientation of helix α4 in NsrR.	RESULTS
+4	14	structures	evidence	The structures of the RD and ED domains of NsrR aligned to other response regulators.	TABLE
+22	24	RD	structure_element	The structures of the RD and ED domains of NsrR aligned to other response regulators.	TABLE
+29	31	ED	structure_element	The structures of the RD and ED domains of NsrR aligned to other response regulators.	TABLE
+43	47	NsrR	protein	The structures of the RD and ED domains of NsrR aligned to other response regulators.	TABLE
+48	55	aligned	experimental_method	The structures of the RD and ED domains of NsrR aligned to other response regulators.	TABLE
+65	84	response regulators	protein_type	The structures of the RD and ED domains of NsrR aligned to other response regulators.	TABLE
+4	8	rmsd	evidence	The rmsd values of the superimpositions of the structures of NsrR-RD and NsrR-ED with the available structures of members of the OmpR/PhoB subfamily are highlighted. *Seq ID (%) corresponds to the full-length protein sequence.	TABLE
+23	39	superimpositions	experimental_method	The rmsd values of the superimpositions of the structures of NsrR-RD and NsrR-ED with the available structures of members of the OmpR/PhoB subfamily are highlighted. *Seq ID (%) corresponds to the full-length protein sequence.	TABLE
+47	57	structures	evidence	The rmsd values of the superimpositions of the structures of NsrR-RD and NsrR-ED with the available structures of members of the OmpR/PhoB subfamily are highlighted. *Seq ID (%) corresponds to the full-length protein sequence.	TABLE
+61	65	NsrR	protein	The rmsd values of the superimpositions of the structures of NsrR-RD and NsrR-ED with the available structures of members of the OmpR/PhoB subfamily are highlighted. *Seq ID (%) corresponds to the full-length protein sequence.	TABLE
+66	68	RD	structure_element	The rmsd values of the superimpositions of the structures of NsrR-RD and NsrR-ED with the available structures of members of the OmpR/PhoB subfamily are highlighted. *Seq ID (%) corresponds to the full-length protein sequence.	TABLE
+73	77	NsrR	protein	The rmsd values of the superimpositions of the structures of NsrR-RD and NsrR-ED with the available structures of members of the OmpR/PhoB subfamily are highlighted. *Seq ID (%) corresponds to the full-length protein sequence.	TABLE
+78	80	ED	structure_element	The rmsd values of the superimpositions of the structures of NsrR-RD and NsrR-ED with the available structures of members of the OmpR/PhoB subfamily are highlighted. *Seq ID (%) corresponds to the full-length protein sequence.	TABLE
+100	110	structures	evidence	The rmsd values of the superimpositions of the structures of NsrR-RD and NsrR-ED with the available structures of members of the OmpR/PhoB subfamily are highlighted. *Seq ID (%) corresponds to the full-length protein sequence.	TABLE
+129	148	OmpR/PhoB subfamily	protein_type	The rmsd values of the superimpositions of the structures of NsrR-RD and NsrR-ED with the available structures of members of the OmpR/PhoB subfamily are highlighted. *Seq ID (%) corresponds to the full-length protein sequence.	TABLE
+197	208	full-length	protein_state	The rmsd values of the superimpositions of the structures of NsrR-RD and NsrR-ED with the available structures of members of the OmpR/PhoB subfamily are highlighted. *Seq ID (%) corresponds to the full-length protein sequence.	TABLE
+13	24	Dali server	experimental_method	Based on the Dali server, the NsrR-RD domain is structurally closely related to KdpE (PDB code: 4KNY) from E. coli, displaying a sequence identity of 28%.	RESULTS
+30	34	NsrR	protein	Based on the Dali server, the NsrR-RD domain is structurally closely related to KdpE (PDB code: 4KNY) from E. coli, displaying a sequence identity of 28%.	RESULTS
+35	37	RD	structure_element	Based on the Dali server, the NsrR-RD domain is structurally closely related to KdpE (PDB code: 4KNY) from E. coli, displaying a sequence identity of 28%.	RESULTS
+80	84	KdpE	protein	Based on the Dali server, the NsrR-RD domain is structurally closely related to KdpE (PDB code: 4KNY) from E. coli, displaying a sequence identity of 28%.	RESULTS
+107	114	E. coli	species	Based on the Dali server, the NsrR-RD domain is structurally closely related to KdpE (PDB code: 4KNY) from E. coli, displaying a sequence identity of 28%.	RESULTS
+54	58	rmsd	evidence	This structural homology is also reflected by the low rmsd of 1.9 Å over 117 Cα atoms after superimposition of the receiver domains of NsrR and KdpE (Table 2).	RESULTS
+92	107	superimposition	experimental_method	This structural homology is also reflected by the low rmsd of 1.9 Å over 117 Cα atoms after superimposition of the receiver domains of NsrR and KdpE (Table 2).	RESULTS
+115	131	receiver domains	structure_element	This structural homology is also reflected by the low rmsd of 1.9 Å over 117 Cα atoms after superimposition of the receiver domains of NsrR and KdpE (Table 2).	RESULTS
+135	139	NsrR	protein	This structural homology is also reflected by the low rmsd of 1.9 Å over 117 Cα atoms after superimposition of the receiver domains of NsrR and KdpE (Table 2).	RESULTS
+144	148	KdpE	protein	This structural homology is also reflected by the low rmsd of 1.9 Å over 117 Cα atoms after superimposition of the receiver domains of NsrR and KdpE (Table 2).	RESULTS
+36	41	helix	structure_element	Furthermore, the orientation of the helix α4 in NsrR is close to that present in KdpE (S1 Fig).	RESULTS
+42	44	α4	structure_element	Furthermore, the orientation of the helix α4 in NsrR is close to that present in KdpE (S1 Fig).	RESULTS
+48	52	NsrR	protein	Furthermore, the orientation of the helix α4 in NsrR is close to that present in KdpE (S1 Fig).	RESULTS
+81	85	KdpE	protein	Furthermore, the orientation of the helix α4 in NsrR is close to that present in KdpE (S1 Fig).	RESULTS
+0	11	Active site	site	Active site residues and dimerization	RESULTS
+4	7	RRs	protein_type	All RRs contain a highly conserved aspartate residue in the active site (Fig 3; shown in red).	RESULTS
+18	34	highly conserved	protein_state	All RRs contain a highly conserved aspartate residue in the active site (Fig 3; shown in red).	RESULTS
+35	44	aspartate	residue_name	All RRs contain a highly conserved aspartate residue in the active site (Fig 3; shown in red).	RESULTS
+60	71	active site	site	All RRs contain a highly conserved aspartate residue in the active site (Fig 3; shown in red).	RESULTS
+0	15	Phosphorylation	ptm	Phosphorylation of this aspartate residue induces a conformational change leading to the activation of the effector domain that binds DNA and regulates the transcription of target genes.	RESULTS
+24	33	aspartate	residue_name	Phosphorylation of this aspartate residue induces a conformational change leading to the activation of the effector domain that binds DNA and regulates the transcription of target genes.	RESULTS
+107	122	effector domain	structure_element	Phosphorylation of this aspartate residue induces a conformational change leading to the activation of the effector domain that binds DNA and regulates the transcription of target genes.	RESULTS
+134	137	DNA	chemical	Phosphorylation of this aspartate residue induces a conformational change leading to the activation of the effector domain that binds DNA and regulates the transcription of target genes.	RESULTS
+13	28	phosphorylation	ptm	This site of phosphorylation is conserved throughout the family of response regulators, including the lantibiotic resistance-associated RRs such as BraR from L. monocytogenes, BceR from Bacillus subtilis, CprR from C. difficile, GraR from S. aureus, LcrR from S. mutans, LisR, and VirR from L. monocytogenes (Fig 3).	RESULTS
+32	41	conserved	protein_state	This site of phosphorylation is conserved throughout the family of response regulators, including the lantibiotic resistance-associated RRs such as BraR from L. monocytogenes, BceR from Bacillus subtilis, CprR from C. difficile, GraR from S. aureus, LcrR from S. mutans, LisR, and VirR from L. monocytogenes (Fig 3).	RESULTS
+67	86	response regulators	protein_type	This site of phosphorylation is conserved throughout the family of response regulators, including the lantibiotic resistance-associated RRs such as BraR from L. monocytogenes, BceR from Bacillus subtilis, CprR from C. difficile, GraR from S. aureus, LcrR from S. mutans, LisR, and VirR from L. monocytogenes (Fig 3).	RESULTS
+102	139	lantibiotic resistance-associated RRs	protein_type	This site of phosphorylation is conserved throughout the family of response regulators, including the lantibiotic resistance-associated RRs such as BraR from L. monocytogenes, BceR from Bacillus subtilis, CprR from C. difficile, GraR from S. aureus, LcrR from S. mutans, LisR, and VirR from L. monocytogenes (Fig 3).	RESULTS
+148	152	BraR	protein	This site of phosphorylation is conserved throughout the family of response regulators, including the lantibiotic resistance-associated RRs such as BraR from L. monocytogenes, BceR from Bacillus subtilis, CprR from C. difficile, GraR from S. aureus, LcrR from S. mutans, LisR, and VirR from L. monocytogenes (Fig 3).	RESULTS
+158	174	L. monocytogenes	species	This site of phosphorylation is conserved throughout the family of response regulators, including the lantibiotic resistance-associated RRs such as BraR from L. monocytogenes, BceR from Bacillus subtilis, CprR from C. difficile, GraR from S. aureus, LcrR from S. mutans, LisR, and VirR from L. monocytogenes (Fig 3).	RESULTS
+176	180	BceR	protein	This site of phosphorylation is conserved throughout the family of response regulators, including the lantibiotic resistance-associated RRs such as BraR from L. monocytogenes, BceR from Bacillus subtilis, CprR from C. difficile, GraR from S. aureus, LcrR from S. mutans, LisR, and VirR from L. monocytogenes (Fig 3).	RESULTS
+186	203	Bacillus subtilis	species	This site of phosphorylation is conserved throughout the family of response regulators, including the lantibiotic resistance-associated RRs such as BraR from L. monocytogenes, BceR from Bacillus subtilis, CprR from C. difficile, GraR from S. aureus, LcrR from S. mutans, LisR, and VirR from L. monocytogenes (Fig 3).	RESULTS
+205	209	CprR	protein	This site of phosphorylation is conserved throughout the family of response regulators, including the lantibiotic resistance-associated RRs such as BraR from L. monocytogenes, BceR from Bacillus subtilis, CprR from C. difficile, GraR from S. aureus, LcrR from S. mutans, LisR, and VirR from L. monocytogenes (Fig 3).	RESULTS
+215	227	C. difficile	species	This site of phosphorylation is conserved throughout the family of response regulators, including the lantibiotic resistance-associated RRs such as BraR from L. monocytogenes, BceR from Bacillus subtilis, CprR from C. difficile, GraR from S. aureus, LcrR from S. mutans, LisR, and VirR from L. monocytogenes (Fig 3).	RESULTS
+229	233	GraR	protein	This site of phosphorylation is conserved throughout the family of response regulators, including the lantibiotic resistance-associated RRs such as BraR from L. monocytogenes, BceR from Bacillus subtilis, CprR from C. difficile, GraR from S. aureus, LcrR from S. mutans, LisR, and VirR from L. monocytogenes (Fig 3).	RESULTS
+239	248	S. aureus	species	This site of phosphorylation is conserved throughout the family of response regulators, including the lantibiotic resistance-associated RRs such as BraR from L. monocytogenes, BceR from Bacillus subtilis, CprR from C. difficile, GraR from S. aureus, LcrR from S. mutans, LisR, and VirR from L. monocytogenes (Fig 3).	RESULTS
+250	254	LcrR	protein	This site of phosphorylation is conserved throughout the family of response regulators, including the lantibiotic resistance-associated RRs such as BraR from L. monocytogenes, BceR from Bacillus subtilis, CprR from C. difficile, GraR from S. aureus, LcrR from S. mutans, LisR, and VirR from L. monocytogenes (Fig 3).	RESULTS
+260	269	S. mutans	species	This site of phosphorylation is conserved throughout the family of response regulators, including the lantibiotic resistance-associated RRs such as BraR from L. monocytogenes, BceR from Bacillus subtilis, CprR from C. difficile, GraR from S. aureus, LcrR from S. mutans, LisR, and VirR from L. monocytogenes (Fig 3).	RESULTS
+271	275	LisR	protein	This site of phosphorylation is conserved throughout the family of response regulators, including the lantibiotic resistance-associated RRs such as BraR from L. monocytogenes, BceR from Bacillus subtilis, CprR from C. difficile, GraR from S. aureus, LcrR from S. mutans, LisR, and VirR from L. monocytogenes (Fig 3).	RESULTS
+281	285	VirR	protein	This site of phosphorylation is conserved throughout the family of response regulators, including the lantibiotic resistance-associated RRs such as BraR from L. monocytogenes, BceR from Bacillus subtilis, CprR from C. difficile, GraR from S. aureus, LcrR from S. mutans, LisR, and VirR from L. monocytogenes (Fig 3).	RESULTS
+291	307	L. monocytogenes	species	This site of phosphorylation is conserved throughout the family of response regulators, including the lantibiotic resistance-associated RRs such as BraR from L. monocytogenes, BceR from Bacillus subtilis, CprR from C. difficile, GraR from S. aureus, LcrR from S. mutans, LisR, and VirR from L. monocytogenes (Fig 3).	RESULTS
+0	18	Sequence alignment	experimental_method	Sequence alignment of NsrR protein with other response regulators.	FIG
+22	26	NsrR	protein	Sequence alignment of NsrR protein with other response regulators.	FIG
+46	65	response regulators	protein_type	Sequence alignment of NsrR protein with other response regulators.	FIG
+2	20	sequence alignment	experimental_method	A sequence alignment of NsrR with RRs belonging to the OmpR/PhoB subfamily (marked in grey) and RRs involved in lantibiotic resistance (black) is shown.	FIG
+24	28	NsrR	protein	A sequence alignment of NsrR with RRs belonging to the OmpR/PhoB subfamily (marked in grey) and RRs involved in lantibiotic resistance (black) is shown.	FIG
+34	37	RRs	protein_type	A sequence alignment of NsrR with RRs belonging to the OmpR/PhoB subfamily (marked in grey) and RRs involved in lantibiotic resistance (black) is shown.	FIG
+55	74	OmpR/PhoB subfamily	protein_type	A sequence alignment of NsrR with RRs belonging to the OmpR/PhoB subfamily (marked in grey) and RRs involved in lantibiotic resistance (black) is shown.	FIG
+96	99	RRs	protein_type	A sequence alignment of NsrR with RRs belonging to the OmpR/PhoB subfamily (marked in grey) and RRs involved in lantibiotic resistance (black) is shown.	FIG
+112	123	lantibiotic	chemical	A sequence alignment of NsrR with RRs belonging to the OmpR/PhoB subfamily (marked in grey) and RRs involved in lantibiotic resistance (black) is shown.	FIG
+4	15	active site	site	The active site aspartate residue (highlighted in red), the residues forming the acidic pocket surrounding it (highlighted in pink), the switch residues (highlighted in blue), the conserved lysine residue (highlighted in green), the highly conserved residues of the linker region (colored in purple), the residues involved in dimer interface of receiver domain (highlighted in yellow), residues involved in interdomain interactions (shown in orange boxes and in cyan) and the residues involved in interaction with DNA (colored in blue) are shown.	FIG
+16	25	aspartate	residue_name	The active site aspartate residue (highlighted in red), the residues forming the acidic pocket surrounding it (highlighted in pink), the switch residues (highlighted in blue), the conserved lysine residue (highlighted in green), the highly conserved residues of the linker region (colored in purple), the residues involved in dimer interface of receiver domain (highlighted in yellow), residues involved in interdomain interactions (shown in orange boxes and in cyan) and the residues involved in interaction with DNA (colored in blue) are shown.	FIG
+81	94	acidic pocket	site	The active site aspartate residue (highlighted in red), the residues forming the acidic pocket surrounding it (highlighted in pink), the switch residues (highlighted in blue), the conserved lysine residue (highlighted in green), the highly conserved residues of the linker region (colored in purple), the residues involved in dimer interface of receiver domain (highlighted in yellow), residues involved in interdomain interactions (shown in orange boxes and in cyan) and the residues involved in interaction with DNA (colored in blue) are shown.	FIG
+137	152	switch residues	site	The active site aspartate residue (highlighted in red), the residues forming the acidic pocket surrounding it (highlighted in pink), the switch residues (highlighted in blue), the conserved lysine residue (highlighted in green), the highly conserved residues of the linker region (colored in purple), the residues involved in dimer interface of receiver domain (highlighted in yellow), residues involved in interdomain interactions (shown in orange boxes and in cyan) and the residues involved in interaction with DNA (colored in blue) are shown.	FIG
+180	189	conserved	protein_state	The active site aspartate residue (highlighted in red), the residues forming the acidic pocket surrounding it (highlighted in pink), the switch residues (highlighted in blue), the conserved lysine residue (highlighted in green), the highly conserved residues of the linker region (colored in purple), the residues involved in dimer interface of receiver domain (highlighted in yellow), residues involved in interdomain interactions (shown in orange boxes and in cyan) and the residues involved in interaction with DNA (colored in blue) are shown.	FIG
+190	196	lysine	residue_name	The active site aspartate residue (highlighted in red), the residues forming the acidic pocket surrounding it (highlighted in pink), the switch residues (highlighted in blue), the conserved lysine residue (highlighted in green), the highly conserved residues of the linker region (colored in purple), the residues involved in dimer interface of receiver domain (highlighted in yellow), residues involved in interdomain interactions (shown in orange boxes and in cyan) and the residues involved in interaction with DNA (colored in blue) are shown.	FIG
+233	249	highly conserved	protein_state	The active site aspartate residue (highlighted in red), the residues forming the acidic pocket surrounding it (highlighted in pink), the switch residues (highlighted in blue), the conserved lysine residue (highlighted in green), the highly conserved residues of the linker region (colored in purple), the residues involved in dimer interface of receiver domain (highlighted in yellow), residues involved in interdomain interactions (shown in orange boxes and in cyan) and the residues involved in interaction with DNA (colored in blue) are shown.	FIG
+266	279	linker region	structure_element	The active site aspartate residue (highlighted in red), the residues forming the acidic pocket surrounding it (highlighted in pink), the switch residues (highlighted in blue), the conserved lysine residue (highlighted in green), the highly conserved residues of the linker region (colored in purple), the residues involved in dimer interface of receiver domain (highlighted in yellow), residues involved in interdomain interactions (shown in orange boxes and in cyan) and the residues involved in interaction with DNA (colored in blue) are shown.	FIG
+326	341	dimer interface	site	The active site aspartate residue (highlighted in red), the residues forming the acidic pocket surrounding it (highlighted in pink), the switch residues (highlighted in blue), the conserved lysine residue (highlighted in green), the highly conserved residues of the linker region (colored in purple), the residues involved in dimer interface of receiver domain (highlighted in yellow), residues involved in interdomain interactions (shown in orange boxes and in cyan) and the residues involved in interaction with DNA (colored in blue) are shown.	FIG
+345	360	receiver domain	structure_element	The active site aspartate residue (highlighted in red), the residues forming the acidic pocket surrounding it (highlighted in pink), the switch residues (highlighted in blue), the conserved lysine residue (highlighted in green), the highly conserved residues of the linker region (colored in purple), the residues involved in dimer interface of receiver domain (highlighted in yellow), residues involved in interdomain interactions (shown in orange boxes and in cyan) and the residues involved in interaction with DNA (colored in blue) are shown.	FIG
+514	517	DNA	chemical	The active site aspartate residue (highlighted in red), the residues forming the acidic pocket surrounding it (highlighted in pink), the switch residues (highlighted in blue), the conserved lysine residue (highlighted in green), the highly conserved residues of the linker region (colored in purple), the residues involved in dimer interface of receiver domain (highlighted in yellow), residues involved in interdomain interactions (shown in orange boxes and in cyan) and the residues involved in interaction with DNA (colored in blue) are shown.	FIG
+4	17	linker region	structure_element	The linker region of the known structures is underlined within the sequence.	FIG
+31	41	structures	evidence	The linker region of the known structures is underlined within the sequence.	FIG
+13	33	phosphorylation site	site	The putative phosphorylation site of NsrR is Asp55, which is localized at the end of strand β3 (Fig 3, shown in red; Fig 4) and lies within an acidic environment composed of the side chains of Glu12 and Asp13 (Fig 3, highlighted in pink).	RESULTS
+37	41	NsrR	protein	The putative phosphorylation site of NsrR is Asp55, which is localized at the end of strand β3 (Fig 3, shown in red; Fig 4) and lies within an acidic environment composed of the side chains of Glu12 and Asp13 (Fig 3, highlighted in pink).	RESULTS
+45	50	Asp55	residue_name_number	The putative phosphorylation site of NsrR is Asp55, which is localized at the end of strand β3 (Fig 3, shown in red; Fig 4) and lies within an acidic environment composed of the side chains of Glu12 and Asp13 (Fig 3, highlighted in pink).	RESULTS
+85	91	strand	structure_element	The putative phosphorylation site of NsrR is Asp55, which is localized at the end of strand β3 (Fig 3, shown in red; Fig 4) and lies within an acidic environment composed of the side chains of Glu12 and Asp13 (Fig 3, highlighted in pink).	RESULTS
+92	94	β3	structure_element	The putative phosphorylation site of NsrR is Asp55, which is localized at the end of strand β3 (Fig 3, shown in red; Fig 4) and lies within an acidic environment composed of the side chains of Glu12 and Asp13 (Fig 3, highlighted in pink).	RESULTS
+193	198	Glu12	residue_name_number	The putative phosphorylation site of NsrR is Asp55, which is localized at the end of strand β3 (Fig 3, shown in red; Fig 4) and lies within an acidic environment composed of the side chains of Glu12 and Asp13 (Fig 3, highlighted in pink).	RESULTS
+203	208	Asp13	residue_name_number	The putative phosphorylation site of NsrR is Asp55, which is localized at the end of strand β3 (Fig 3, shown in red; Fig 4) and lies within an acidic environment composed of the side chains of Glu12 and Asp13 (Fig 3, highlighted in pink).	RESULTS
+5	11	pocket	site	This pocket is similar to the acidic active site observed within most structures of RRs such as PhoB from E. coli, PhoP from M. tuberculosis, and DivK from Caulobacter crescentus.	RESULTS
+30	36	acidic	protein_state	This pocket is similar to the acidic active site observed within most structures of RRs such as PhoB from E. coli, PhoP from M. tuberculosis, and DivK from Caulobacter crescentus.	RESULTS
+37	48	active site	site	This pocket is similar to the acidic active site observed within most structures of RRs such as PhoB from E. coli, PhoP from M. tuberculosis, and DivK from Caulobacter crescentus.	RESULTS
+70	80	structures	evidence	This pocket is similar to the acidic active site observed within most structures of RRs such as PhoB from E. coli, PhoP from M. tuberculosis, and DivK from Caulobacter crescentus.	RESULTS
+84	87	RRs	protein_type	This pocket is similar to the acidic active site observed within most structures of RRs such as PhoB from E. coli, PhoP from M. tuberculosis, and DivK from Caulobacter crescentus.	RESULTS
+96	100	PhoB	protein	This pocket is similar to the acidic active site observed within most structures of RRs such as PhoB from E. coli, PhoP from M. tuberculosis, and DivK from Caulobacter crescentus.	RESULTS
+106	113	E. coli	species	This pocket is similar to the acidic active site observed within most structures of RRs such as PhoB from E. coli, PhoP from M. tuberculosis, and DivK from Caulobacter crescentus.	RESULTS
+115	119	PhoP	protein	This pocket is similar to the acidic active site observed within most structures of RRs such as PhoB from E. coli, PhoP from M. tuberculosis, and DivK from Caulobacter crescentus.	RESULTS
+125	140	M. tuberculosis	species	This pocket is similar to the acidic active site observed within most structures of RRs such as PhoB from E. coli, PhoP from M. tuberculosis, and DivK from Caulobacter crescentus.	RESULTS
+146	150	DivK	protein	This pocket is similar to the acidic active site observed within most structures of RRs such as PhoB from E. coli, PhoP from M. tuberculosis, and DivK from Caulobacter crescentus.	RESULTS
+156	178	Caulobacter crescentus	species	This pocket is similar to the acidic active site observed within most structures of RRs such as PhoB from E. coli, PhoP from M. tuberculosis, and DivK from Caulobacter crescentus.	RESULTS
+3	7	NsrR	protein	In NsrR, Glu12, Asp13, and Asp55 are in close proximity of a highly conserved Lys104 residue (highlighted in green in Fig 3).	RESULTS
+9	14	Glu12	residue_name_number	In NsrR, Glu12, Asp13, and Asp55 are in close proximity of a highly conserved Lys104 residue (highlighted in green in Fig 3).	RESULTS
+16	21	Asp13	residue_name_number	In NsrR, Glu12, Asp13, and Asp55 are in close proximity of a highly conserved Lys104 residue (highlighted in green in Fig 3).	RESULTS
+27	32	Asp55	residue_name_number	In NsrR, Glu12, Asp13, and Asp55 are in close proximity of a highly conserved Lys104 residue (highlighted in green in Fig 3).	RESULTS
+61	77	highly conserved	protein_state	In NsrR, Glu12, Asp13, and Asp55 are in close proximity of a highly conserved Lys104 residue (highlighted in green in Fig 3).	RESULTS
+78	84	Lys104	residue_name_number	In NsrR, Glu12, Asp13, and Asp55 are in close proximity of a highly conserved Lys104 residue (highlighted in green in Fig 3).	RESULTS
+16	32	highly conserved	protein_state	Location of the highly conserved Asp55 and inactive state conformation of the key switch residues, Ser82 and Phe101 in NsrR-RD.	FIG
+33	38	Asp55	residue_name_number	Location of the highly conserved Asp55 and inactive state conformation of the key switch residues, Ser82 and Phe101 in NsrR-RD.	FIG
+43	51	inactive	protein_state	Location of the highly conserved Asp55 and inactive state conformation of the key switch residues, Ser82 and Phe101 in NsrR-RD.	FIG
+82	97	switch residues	site	Location of the highly conserved Asp55 and inactive state conformation of the key switch residues, Ser82 and Phe101 in NsrR-RD.	FIG
+99	104	Ser82	residue_name_number	Location of the highly conserved Asp55 and inactive state conformation of the key switch residues, Ser82 and Phe101 in NsrR-RD.	FIG
+109	115	Phe101	residue_name_number	Location of the highly conserved Asp55 and inactive state conformation of the key switch residues, Ser82 and Phe101 in NsrR-RD.	FIG
+119	123	NsrR	protein	Location of the highly conserved Asp55 and inactive state conformation of the key switch residues, Ser82 and Phe101 in NsrR-RD.	FIG
+124	126	RD	structure_element	Location of the highly conserved Asp55 and inactive state conformation of the key switch residues, Ser82 and Phe101 in NsrR-RD.	FIG
+0	4	NsrR	protein	NsrR (represented in yellow) displays a geometry representing the inactive state as deduced from the inactive state structure of PhoB (shown in brown, PDB code 1B00) (a).	FIG
+66	74	inactive	protein_state	NsrR (represented in yellow) displays a geometry representing the inactive state as deduced from the inactive state structure of PhoB (shown in brown, PDB code 1B00) (a).	FIG
+101	109	inactive	protein_state	NsrR (represented in yellow) displays a geometry representing the inactive state as deduced from the inactive state structure of PhoB (shown in brown, PDB code 1B00) (a).	FIG
+116	125	structure	evidence	NsrR (represented in yellow) displays a geometry representing the inactive state as deduced from the inactive state structure of PhoB (shown in brown, PDB code 1B00) (a).	FIG
+129	133	PhoB	protein	NsrR (represented in yellow) displays a geometry representing the inactive state as deduced from the inactive state structure of PhoB (shown in brown, PDB code 1B00) (a).	FIG
+4	12	inactive	protein_state	The inactive conformation of NsrR differs from the active state structure of PhoB (light blue, PDB code 1ZES) (b) in the orientation of the corresponding switch residues, Ser82 and Phe101, which adopt a conformation pointing away from the active site (Asp55 in NsrR).	FIG
+29	33	NsrR	protein	The inactive conformation of NsrR differs from the active state structure of PhoB (light blue, PDB code 1ZES) (b) in the orientation of the corresponding switch residues, Ser82 and Phe101, which adopt a conformation pointing away from the active site (Asp55 in NsrR).	FIG
+51	57	active	protein_state	The inactive conformation of NsrR differs from the active state structure of PhoB (light blue, PDB code 1ZES) (b) in the orientation of the corresponding switch residues, Ser82 and Phe101, which adopt a conformation pointing away from the active site (Asp55 in NsrR).	FIG
+64	73	structure	evidence	The inactive conformation of NsrR differs from the active state structure of PhoB (light blue, PDB code 1ZES) (b) in the orientation of the corresponding switch residues, Ser82 and Phe101, which adopt a conformation pointing away from the active site (Asp55 in NsrR).	FIG
+77	81	PhoB	protein	The inactive conformation of NsrR differs from the active state structure of PhoB (light blue, PDB code 1ZES) (b) in the orientation of the corresponding switch residues, Ser82 and Phe101, which adopt a conformation pointing away from the active site (Asp55 in NsrR).	FIG
+154	169	switch residues	site	The inactive conformation of NsrR differs from the active state structure of PhoB (light blue, PDB code 1ZES) (b) in the orientation of the corresponding switch residues, Ser82 and Phe101, which adopt a conformation pointing away from the active site (Asp55 in NsrR).	FIG
+171	176	Ser82	residue_name_number	The inactive conformation of NsrR differs from the active state structure of PhoB (light blue, PDB code 1ZES) (b) in the orientation of the corresponding switch residues, Ser82 and Phe101, which adopt a conformation pointing away from the active site (Asp55 in NsrR).	FIG
+181	187	Phe101	residue_name_number	The inactive conformation of NsrR differs from the active state structure of PhoB (light blue, PDB code 1ZES) (b) in the orientation of the corresponding switch residues, Ser82 and Phe101, which adopt a conformation pointing away from the active site (Asp55 in NsrR).	FIG
+239	250	active site	site	The inactive conformation of NsrR differs from the active state structure of PhoB (light blue, PDB code 1ZES) (b) in the orientation of the corresponding switch residues, Ser82 and Phe101, which adopt a conformation pointing away from the active site (Asp55 in NsrR).	FIG
+252	257	Asp55	residue_name_number	The inactive conformation of NsrR differs from the active state structure of PhoB (light blue, PDB code 1ZES) (b) in the orientation of the corresponding switch residues, Ser82 and Phe101, which adopt a conformation pointing away from the active site (Asp55 in NsrR).	FIG
+261	265	NsrR	protein	The inactive conformation of NsrR differs from the active state structure of PhoB (light blue, PDB code 1ZES) (b) in the orientation of the corresponding switch residues, Ser82 and Phe101, which adopt a conformation pointing away from the active site (Asp55 in NsrR).	FIG
+86	101	phosphorylation	ptm	A divalent metal ion is usually bound in this acidic environment and is essential for phosphorylation and de-phosphorylation of RRs.	RESULTS
+106	124	de-phosphorylation	ptm	A divalent metal ion is usually bound in this acidic environment and is essential for phosphorylation and de-phosphorylation of RRs.	RESULTS
+128	131	RRs	protein_type	A divalent metal ion is usually bound in this acidic environment and is essential for phosphorylation and de-phosphorylation of RRs.	RESULTS
+8	11	RRs	protein_type	In some RRs like CheY, Mg2+ is observed in the structure, bound near the phosphorylation site.	RESULTS
+17	21	CheY	protein	In some RRs like CheY, Mg2+ is observed in the structure, bound near the phosphorylation site.	RESULTS
+23	27	Mg2+	chemical	In some RRs like CheY, Mg2+ is observed in the structure, bound near the phosphorylation site.	RESULTS
+47	56	structure	evidence	In some RRs like CheY, Mg2+ is observed in the structure, bound near the phosphorylation site.	RESULTS
+58	63	bound	protein_state	In some RRs like CheY, Mg2+ is observed in the structure, bound near the phosphorylation site.	RESULTS
+73	93	phosphorylation site	site	In some RRs like CheY, Mg2+ is observed in the structure, bound near the phosphorylation site.	RESULTS
+7	11	KdpE	protein	In the KdpE regulator from E. coli that is involved in osmoregulation, a divalent calcium ion is present.	RESULTS
+12	21	regulator	protein_type	In the KdpE regulator from E. coli that is involved in osmoregulation, a divalent calcium ion is present.	RESULTS
+27	34	E. coli	species	In the KdpE regulator from E. coli that is involved in osmoregulation, a divalent calcium ion is present.	RESULTS
+82	89	calcium	chemical	In the KdpE regulator from E. coli that is involved in osmoregulation, a divalent calcium ion is present.	RESULTS
+13	22	structure	evidence	However, the structure of NsrR-RD did not contain any divalent ion.	RESULTS
+26	30	NsrR	protein	However, the structure of NsrR-RD did not contain any divalent ion.	RESULTS
+31	33	RD	structure_element	However, the structure of NsrR-RD did not contain any divalent ion.	RESULTS
+11	16	water	chemical	Instead, a water molecule is present, which interacts with Glu12 of the acidic pocket, Lys104, and another water molecule in the vicinity.	RESULTS
+59	64	Glu12	residue_name_number	Instead, a water molecule is present, which interacts with Glu12 of the acidic pocket, Lys104, and another water molecule in the vicinity.	RESULTS
+72	85	acidic pocket	site	Instead, a water molecule is present, which interacts with Glu12 of the acidic pocket, Lys104, and another water molecule in the vicinity.	RESULTS
+87	93	Lys104	residue_name_number	Instead, a water molecule is present, which interacts with Glu12 of the acidic pocket, Lys104, and another water molecule in the vicinity.	RESULTS
+107	112	water	chemical	Instead, a water molecule is present, which interacts with Glu12 of the acidic pocket, Lys104, and another water molecule in the vicinity.	RESULTS
+11	21	β4-α4 loop	structure_element	Within the β4-α4 loop and in β5 of the RD of RRs, specific amino acids are crucial for signal transduction from the RD to the ED via conformational changes that are a consequence of phosphorylation of the RD.	RESULTS
+29	31	β5	structure_element	Within the β4-α4 loop and in β5 of the RD of RRs, specific amino acids are crucial for signal transduction from the RD to the ED via conformational changes that are a consequence of phosphorylation of the RD.	RESULTS
+39	41	RD	structure_element	Within the β4-α4 loop and in β5 of the RD of RRs, specific amino acids are crucial for signal transduction from the RD to the ED via conformational changes that are a consequence of phosphorylation of the RD.	RESULTS
+45	48	RRs	protein_type	Within the β4-α4 loop and in β5 of the RD of RRs, specific amino acids are crucial for signal transduction from the RD to the ED via conformational changes that are a consequence of phosphorylation of the RD.	RESULTS
+116	118	RD	structure_element	Within the β4-α4 loop and in β5 of the RD of RRs, specific amino acids are crucial for signal transduction from the RD to the ED via conformational changes that are a consequence of phosphorylation of the RD.	RESULTS
+126	128	ED	structure_element	Within the β4-α4 loop and in β5 of the RD of RRs, specific amino acids are crucial for signal transduction from the RD to the ED via conformational changes that are a consequence of phosphorylation of the RD.	RESULTS
+182	197	phosphorylation	ptm	Within the β4-α4 loop and in β5 of the RD of RRs, specific amino acids are crucial for signal transduction from the RD to the ED via conformational changes that are a consequence of phosphorylation of the RD.	RESULTS
+205	207	RD	structure_element	Within the β4-α4 loop and in β5 of the RD of RRs, specific amino acids are crucial for signal transduction from the RD to the ED via conformational changes that are a consequence of phosphorylation of the RD.	RESULTS
+22	25	Ser	residue_name	These amino acids are Ser/Thr and Phe/Tyr located at the end of β4 and before β5, respectively, and designated as “signature switch residues”.	RESULTS
+26	29	Thr	residue_name	These amino acids are Ser/Thr and Phe/Tyr located at the end of β4 and before β5, respectively, and designated as “signature switch residues”.	RESULTS
+34	37	Phe	residue_name	These amino acids are Ser/Thr and Phe/Tyr located at the end of β4 and before β5, respectively, and designated as “signature switch residues”.	RESULTS
+38	41	Tyr	residue_name	These amino acids are Ser/Thr and Phe/Tyr located at the end of β4 and before β5, respectively, and designated as “signature switch residues”.	RESULTS
+64	66	β4	structure_element	These amino acids are Ser/Thr and Phe/Tyr located at the end of β4 and before β5, respectively, and designated as “signature switch residues”.	RESULTS
+78	80	β5	structure_element	These amino acids are Ser/Thr and Phe/Tyr located at the end of β4 and before β5, respectively, and designated as “signature switch residues”.	RESULTS
+115	140	signature switch residues	site	These amino acids are Ser/Thr and Phe/Tyr located at the end of β4 and before β5, respectively, and designated as “signature switch residues”.	RESULTS
+15	24	alignment	experimental_method	As seen in the alignment (Fig 3, highlighted in blue), these signature residues (Ser/Thr and Phe/Tyr) are highly conserved in the lantibiotic resistance-associated RRs.	RESULTS
+81	84	Ser	residue_name	As seen in the alignment (Fig 3, highlighted in blue), these signature residues (Ser/Thr and Phe/Tyr) are highly conserved in the lantibiotic resistance-associated RRs.	RESULTS
+85	88	Thr	residue_name	As seen in the alignment (Fig 3, highlighted in blue), these signature residues (Ser/Thr and Phe/Tyr) are highly conserved in the lantibiotic resistance-associated RRs.	RESULTS
+93	96	Phe	residue_name	As seen in the alignment (Fig 3, highlighted in blue), these signature residues (Ser/Thr and Phe/Tyr) are highly conserved in the lantibiotic resistance-associated RRs.	RESULTS
+97	100	Tyr	residue_name	As seen in the alignment (Fig 3, highlighted in blue), these signature residues (Ser/Thr and Phe/Tyr) are highly conserved in the lantibiotic resistance-associated RRs.	RESULTS
+106	122	highly conserved	protein_state	As seen in the alignment (Fig 3, highlighted in blue), these signature residues (Ser/Thr and Phe/Tyr) are highly conserved in the lantibiotic resistance-associated RRs.	RESULTS
+130	167	lantibiotic resistance-associated RRs	protein_type	As seen in the alignment (Fig 3, highlighted in blue), these signature residues (Ser/Thr and Phe/Tyr) are highly conserved in the lantibiotic resistance-associated RRs.	RESULTS
+76	78	RD	structure_element	The orientation of the side chains of these residues determines whether the RD is in an active or inactive state.	RESULTS
+88	94	active	protein_state	The orientation of the side chains of these residues determines whether the RD is in an active or inactive state.	RESULTS
+98	106	inactive	protein_state	The orientation of the side chains of these residues determines whether the RD is in an active or inactive state.	RESULTS
+7	15	inactive	protein_state	In the inactive state, the phenylalanine or tyrosine residue faces away from the active site, and the corresponding serine or threonine residue adopts an outward-facing conformation as well (Fig 4A).	RESULTS
+27	40	phenylalanine	residue_name	In the inactive state, the phenylalanine or tyrosine residue faces away from the active site, and the corresponding serine or threonine residue adopts an outward-facing conformation as well (Fig 4A).	RESULTS
+44	52	tyrosine	residue_name	In the inactive state, the phenylalanine or tyrosine residue faces away from the active site, and the corresponding serine or threonine residue adopts an outward-facing conformation as well (Fig 4A).	RESULTS
+81	92	active site	site	In the inactive state, the phenylalanine or tyrosine residue faces away from the active site, and the corresponding serine or threonine residue adopts an outward-facing conformation as well (Fig 4A).	RESULTS
+116	122	serine	residue_name	In the inactive state, the phenylalanine or tyrosine residue faces away from the active site, and the corresponding serine or threonine residue adopts an outward-facing conformation as well (Fig 4A).	RESULTS
+126	135	threonine	residue_name	In the inactive state, the phenylalanine or tyrosine residue faces away from the active site, and the corresponding serine or threonine residue adopts an outward-facing conformation as well (Fig 4A).	RESULTS
+154	168	outward-facing	protein_state	In the inactive state, the phenylalanine or tyrosine residue faces away from the active site, and the corresponding serine or threonine residue adopts an outward-facing conformation as well (Fig 4A).	RESULTS
+17	32	switch residues	site	In contrast, the switch residues face towards the active site in the active state conformation (Fig 4B).	RESULTS
+50	61	active site	site	In contrast, the switch residues face towards the active site in the active state conformation (Fig 4B).	RESULTS
+69	75	active	protein_state	In contrast, the switch residues face towards the active site in the active state conformation (Fig 4B).	RESULTS
+3	21	sequence alignment	experimental_method	By sequence alignment with other lantibiotic resistance-associated RRs, these “signature switch residues” are identified as Ser82 and Phe101 in NsrR (see above).	RESULTS
+33	70	lantibiotic resistance-associated RRs	protein_type	By sequence alignment with other lantibiotic resistance-associated RRs, these “signature switch residues” are identified as Ser82 and Phe101 in NsrR (see above).	RESULTS
+79	104	signature switch residues	site	By sequence alignment with other lantibiotic resistance-associated RRs, these “signature switch residues” are identified as Ser82 and Phe101 in NsrR (see above).	RESULTS
+124	129	Ser82	residue_name_number	By sequence alignment with other lantibiotic resistance-associated RRs, these “signature switch residues” are identified as Ser82 and Phe101 in NsrR (see above).	RESULTS
+134	140	Phe101	residue_name_number	By sequence alignment with other lantibiotic resistance-associated RRs, these “signature switch residues” are identified as Ser82 and Phe101 in NsrR (see above).	RESULTS
+144	148	NsrR	protein	By sequence alignment with other lantibiotic resistance-associated RRs, these “signature switch residues” are identified as Ser82 and Phe101 in NsrR (see above).	RESULTS
+14	17	RRs	protein_type	Although some RRs such as KdpE, BraR, BceR, GraR, and VirR contain a serine residue as the first switch residue, the others possess a threonine instead.	RESULTS
+26	30	KdpE	protein	Although some RRs such as KdpE, BraR, BceR, GraR, and VirR contain a serine residue as the first switch residue, the others possess a threonine instead.	RESULTS
+32	36	BraR	protein	Although some RRs such as KdpE, BraR, BceR, GraR, and VirR contain a serine residue as the first switch residue, the others possess a threonine instead.	RESULTS
+38	42	BceR	protein	Although some RRs such as KdpE, BraR, BceR, GraR, and VirR contain a serine residue as the first switch residue, the others possess a threonine instead.	RESULTS
+44	48	GraR	protein	Although some RRs such as KdpE, BraR, BceR, GraR, and VirR contain a serine residue as the first switch residue, the others possess a threonine instead.	RESULTS
+54	58	VirR	protein	Although some RRs such as KdpE, BraR, BceR, GraR, and VirR contain a serine residue as the first switch residue, the others possess a threonine instead.	RESULTS
+69	75	serine	residue_name	Although some RRs such as KdpE, BraR, BceR, GraR, and VirR contain a serine residue as the first switch residue, the others possess a threonine instead.	RESULTS
+91	111	first switch residue	site	Although some RRs such as KdpE, BraR, BceR, GraR, and VirR contain a serine residue as the first switch residue, the others possess a threonine instead.	RESULTS
+134	143	threonine	residue_name	Although some RRs such as KdpE, BraR, BceR, GraR, and VirR contain a serine residue as the first switch residue, the others possess a threonine instead.	RESULTS
+17	38	second switch residue	site	Furthermore, the second switch residue is mostly a tyrosine, with NsrR, BraR, and BceR being the only exceptions containing a phenylalanine at that position.	RESULTS
+51	59	tyrosine	residue_name	Furthermore, the second switch residue is mostly a tyrosine, with NsrR, BraR, and BceR being the only exceptions containing a phenylalanine at that position.	RESULTS
+66	70	NsrR	protein	Furthermore, the second switch residue is mostly a tyrosine, with NsrR, BraR, and BceR being the only exceptions containing a phenylalanine at that position.	RESULTS
+72	76	BraR	protein	Furthermore, the second switch residue is mostly a tyrosine, with NsrR, BraR, and BceR being the only exceptions containing a phenylalanine at that position.	RESULTS
+82	86	BceR	protein	Furthermore, the second switch residue is mostly a tyrosine, with NsrR, BraR, and BceR being the only exceptions containing a phenylalanine at that position.	RESULTS
+126	139	phenylalanine	residue_name	Furthermore, the second switch residue is mostly a tyrosine, with NsrR, BraR, and BceR being the only exceptions containing a phenylalanine at that position.	RESULTS
+20	24	NsrR	protein	A comparison of the NsrR-RD structure with the available structures of PhoB (Fig 4) in the active (PDB code: 1ZES) and inactive (PDB code: 1B00) states demonstrates that Ser82 (NsrR-RD) is oriented away from the active site Asp55, and that Phe101 is also in an outward conformation suggesting an inactive state of the NsrR-RD (Fig 4A).	RESULTS
+25	27	RD	structure_element	A comparison of the NsrR-RD structure with the available structures of PhoB (Fig 4) in the active (PDB code: 1ZES) and inactive (PDB code: 1B00) states demonstrates that Ser82 (NsrR-RD) is oriented away from the active site Asp55, and that Phe101 is also in an outward conformation suggesting an inactive state of the NsrR-RD (Fig 4A).	RESULTS
+28	37	structure	evidence	A comparison of the NsrR-RD structure with the available structures of PhoB (Fig 4) in the active (PDB code: 1ZES) and inactive (PDB code: 1B00) states demonstrates that Ser82 (NsrR-RD) is oriented away from the active site Asp55, and that Phe101 is also in an outward conformation suggesting an inactive state of the NsrR-RD (Fig 4A).	RESULTS
+57	67	structures	evidence	A comparison of the NsrR-RD structure with the available structures of PhoB (Fig 4) in the active (PDB code: 1ZES) and inactive (PDB code: 1B00) states demonstrates that Ser82 (NsrR-RD) is oriented away from the active site Asp55, and that Phe101 is also in an outward conformation suggesting an inactive state of the NsrR-RD (Fig 4A).	RESULTS
+71	75	PhoB	protein	A comparison of the NsrR-RD structure with the available structures of PhoB (Fig 4) in the active (PDB code: 1ZES) and inactive (PDB code: 1B00) states demonstrates that Ser82 (NsrR-RD) is oriented away from the active site Asp55, and that Phe101 is also in an outward conformation suggesting an inactive state of the NsrR-RD (Fig 4A).	RESULTS
+91	97	active	protein_state	A comparison of the NsrR-RD structure with the available structures of PhoB (Fig 4) in the active (PDB code: 1ZES) and inactive (PDB code: 1B00) states demonstrates that Ser82 (NsrR-RD) is oriented away from the active site Asp55, and that Phe101 is also in an outward conformation suggesting an inactive state of the NsrR-RD (Fig 4A).	RESULTS
+119	127	inactive	protein_state	A comparison of the NsrR-RD structure with the available structures of PhoB (Fig 4) in the active (PDB code: 1ZES) and inactive (PDB code: 1B00) states demonstrates that Ser82 (NsrR-RD) is oriented away from the active site Asp55, and that Phe101 is also in an outward conformation suggesting an inactive state of the NsrR-RD (Fig 4A).	RESULTS
+170	175	Ser82	residue_name_number	A comparison of the NsrR-RD structure with the available structures of PhoB (Fig 4) in the active (PDB code: 1ZES) and inactive (PDB code: 1B00) states demonstrates that Ser82 (NsrR-RD) is oriented away from the active site Asp55, and that Phe101 is also in an outward conformation suggesting an inactive state of the NsrR-RD (Fig 4A).	RESULTS
+177	181	NsrR	protein	A comparison of the NsrR-RD structure with the available structures of PhoB (Fig 4) in the active (PDB code: 1ZES) and inactive (PDB code: 1B00) states demonstrates that Ser82 (NsrR-RD) is oriented away from the active site Asp55, and that Phe101 is also in an outward conformation suggesting an inactive state of the NsrR-RD (Fig 4A).	RESULTS
+182	184	RD	structure_element	A comparison of the NsrR-RD structure with the available structures of PhoB (Fig 4) in the active (PDB code: 1ZES) and inactive (PDB code: 1B00) states demonstrates that Ser82 (NsrR-RD) is oriented away from the active site Asp55, and that Phe101 is also in an outward conformation suggesting an inactive state of the NsrR-RD (Fig 4A).	RESULTS
+212	223	active site	site	A comparison of the NsrR-RD structure with the available structures of PhoB (Fig 4) in the active (PDB code: 1ZES) and inactive (PDB code: 1B00) states demonstrates that Ser82 (NsrR-RD) is oriented away from the active site Asp55, and that Phe101 is also in an outward conformation suggesting an inactive state of the NsrR-RD (Fig 4A).	RESULTS
+224	229	Asp55	residue_name_number	A comparison of the NsrR-RD structure with the available structures of PhoB (Fig 4) in the active (PDB code: 1ZES) and inactive (PDB code: 1B00) states demonstrates that Ser82 (NsrR-RD) is oriented away from the active site Asp55, and that Phe101 is also in an outward conformation suggesting an inactive state of the NsrR-RD (Fig 4A).	RESULTS
+240	246	Phe101	residue_name_number	A comparison of the NsrR-RD structure with the available structures of PhoB (Fig 4) in the active (PDB code: 1ZES) and inactive (PDB code: 1B00) states demonstrates that Ser82 (NsrR-RD) is oriented away from the active site Asp55, and that Phe101 is also in an outward conformation suggesting an inactive state of the NsrR-RD (Fig 4A).	RESULTS
+261	268	outward	protein_state	A comparison of the NsrR-RD structure with the available structures of PhoB (Fig 4) in the active (PDB code: 1ZES) and inactive (PDB code: 1B00) states demonstrates that Ser82 (NsrR-RD) is oriented away from the active site Asp55, and that Phe101 is also in an outward conformation suggesting an inactive state of the NsrR-RD (Fig 4A).	RESULTS
+296	304	inactive	protein_state	A comparison of the NsrR-RD structure with the available structures of PhoB (Fig 4) in the active (PDB code: 1ZES) and inactive (PDB code: 1B00) states demonstrates that Ser82 (NsrR-RD) is oriented away from the active site Asp55, and that Phe101 is also in an outward conformation suggesting an inactive state of the NsrR-RD (Fig 4A).	RESULTS
+318	322	NsrR	protein	A comparison of the NsrR-RD structure with the available structures of PhoB (Fig 4) in the active (PDB code: 1ZES) and inactive (PDB code: 1B00) states demonstrates that Ser82 (NsrR-RD) is oriented away from the active site Asp55, and that Phe101 is also in an outward conformation suggesting an inactive state of the NsrR-RD (Fig 4A).	RESULTS
+323	325	RD	structure_element	A comparison of the NsrR-RD structure with the available structures of PhoB (Fig 4) in the active (PDB code: 1ZES) and inactive (PDB code: 1B00) states demonstrates that Ser82 (NsrR-RD) is oriented away from the active site Asp55, and that Phe101 is also in an outward conformation suggesting an inactive state of the NsrR-RD (Fig 4A).	RESULTS
+20	23	RRs	protein_type	As mentioned above, RRs contain a phosphorylation-activated switch and normally exist in equilibrium between the active and inactive conformations.	RESULTS
+34	59	phosphorylation-activated	protein_state	As mentioned above, RRs contain a phosphorylation-activated switch and normally exist in equilibrium between the active and inactive conformations.	RESULTS
+60	66	switch	site	As mentioned above, RRs contain a phosphorylation-activated switch and normally exist in equilibrium between the active and inactive conformations.	RESULTS
+113	119	active	protein_state	As mentioned above, RRs contain a phosphorylation-activated switch and normally exist in equilibrium between the active and inactive conformations.	RESULTS
+124	132	inactive	protein_state	As mentioned above, RRs contain a phosphorylation-activated switch and normally exist in equilibrium between the active and inactive conformations.	RESULTS
+0	15	Phosphorylation	ptm	Phosphorylation shifts the equilibrium towards the active conformation and induces the formation of rotationally symmetric dimers on the α4-β5-α5 interface of RDs.	RESULTS
+51	57	active	protein_state	Phosphorylation shifts the equilibrium towards the active conformation and induces the formation of rotationally symmetric dimers on the α4-β5-α5 interface of RDs.	RESULTS
+123	129	dimers	oligomeric_state	Phosphorylation shifts the equilibrium towards the active conformation and induces the formation of rotationally symmetric dimers on the α4-β5-α5 interface of RDs.	RESULTS
+137	155	α4-β5-α5 interface	site	Phosphorylation shifts the equilibrium towards the active conformation and induces the formation of rotationally symmetric dimers on the α4-β5-α5 interface of RDs.	RESULTS
+159	162	RDs	structure_element	Phosphorylation shifts the equilibrium towards the active conformation and induces the formation of rotationally symmetric dimers on the α4-β5-α5 interface of RDs.	RESULTS
+55	58	DNA	chemical	It has been suggested that dimerization is crucial for DNA-binding of RRs of the OmpR/PhoB subfamily.	RESULTS
+70	73	RRs	protein_type	It has been suggested that dimerization is crucial for DNA-binding of RRs of the OmpR/PhoB subfamily.	RESULTS
+81	100	OmpR/PhoB subfamily	protein_type	It has been suggested that dimerization is crucial for DNA-binding of RRs of the OmpR/PhoB subfamily.	RESULTS
+4	6	RD	structure_element	The RD domain of NsrR was crystallized with two separate monomers in the asymmetric unit.	RESULTS
+17	21	NsrR	protein	The RD domain of NsrR was crystallized with two separate monomers in the asymmetric unit.	RESULTS
+26	38	crystallized	experimental_method	The RD domain of NsrR was crystallized with two separate monomers in the asymmetric unit.	RESULTS
+57	65	monomers	oligomeric_state	The RD domain of NsrR was crystallized with two separate monomers in the asymmetric unit.	RESULTS
+26	37	DALI search	experimental_method	Therefore, we performed a DALI search and focused on RD domains that were structurally determined as functional dimers.	RESULTS
+53	55	RD	structure_element	Therefore, we performed a DALI search and focused on RD domains that were structurally determined as functional dimers.	RESULTS
+101	111	functional	protein_state	Therefore, we performed a DALI search and focused on RD domains that were structurally determined as functional dimers.	RESULTS
+112	118	dimers	oligomeric_state	Therefore, we performed a DALI search and focused on RD domains that were structurally determined as functional dimers.	RESULTS
+21	26	dimer	oligomeric_state	In this context, the dimer of full-length KdpE from E. coli (Z-score 18.8, rmsd 1.9 Å over 117 Cα atoms) (PDB code: 4KNY) and the structure of the functional dimer of the RD of KdpE from E. coli (PDB code: 1ZH2) represent the most structurally related structures.	RESULTS
+30	41	full-length	protein_state	In this context, the dimer of full-length KdpE from E. coli (Z-score 18.8, rmsd 1.9 Å over 117 Cα atoms) (PDB code: 4KNY) and the structure of the functional dimer of the RD of KdpE from E. coli (PDB code: 1ZH2) represent the most structurally related structures.	RESULTS
+42	46	KdpE	protein	In this context, the dimer of full-length KdpE from E. coli (Z-score 18.8, rmsd 1.9 Å over 117 Cα atoms) (PDB code: 4KNY) and the structure of the functional dimer of the RD of KdpE from E. coli (PDB code: 1ZH2) represent the most structurally related structures.	RESULTS
+52	59	E. coli	species	In this context, the dimer of full-length KdpE from E. coli (Z-score 18.8, rmsd 1.9 Å over 117 Cα atoms) (PDB code: 4KNY) and the structure of the functional dimer of the RD of KdpE from E. coli (PDB code: 1ZH2) represent the most structurally related structures.	RESULTS
+61	68	Z-score	evidence	In this context, the dimer of full-length KdpE from E. coli (Z-score 18.8, rmsd 1.9 Å over 117 Cα atoms) (PDB code: 4KNY) and the structure of the functional dimer of the RD of KdpE from E. coli (PDB code: 1ZH2) represent the most structurally related structures.	RESULTS
+75	79	rmsd	evidence	In this context, the dimer of full-length KdpE from E. coli (Z-score 18.8, rmsd 1.9 Å over 117 Cα atoms) (PDB code: 4KNY) and the structure of the functional dimer of the RD of KdpE from E. coli (PDB code: 1ZH2) represent the most structurally related structures.	RESULTS
+130	139	structure	evidence	In this context, the dimer of full-length KdpE from E. coli (Z-score 18.8, rmsd 1.9 Å over 117 Cα atoms) (PDB code: 4KNY) and the structure of the functional dimer of the RD of KdpE from E. coli (PDB code: 1ZH2) represent the most structurally related structures.	RESULTS
+147	157	functional	protein_state	In this context, the dimer of full-length KdpE from E. coli (Z-score 18.8, rmsd 1.9 Å over 117 Cα atoms) (PDB code: 4KNY) and the structure of the functional dimer of the RD of KdpE from E. coli (PDB code: 1ZH2) represent the most structurally related structures.	RESULTS
+158	163	dimer	oligomeric_state	In this context, the dimer of full-length KdpE from E. coli (Z-score 18.8, rmsd 1.9 Å over 117 Cα atoms) (PDB code: 4KNY) and the structure of the functional dimer of the RD of KdpE from E. coli (PDB code: 1ZH2) represent the most structurally related structures.	RESULTS
+171	173	RD	structure_element	In this context, the dimer of full-length KdpE from E. coli (Z-score 18.8, rmsd 1.9 Å over 117 Cα atoms) (PDB code: 4KNY) and the structure of the functional dimer of the RD of KdpE from E. coli (PDB code: 1ZH2) represent the most structurally related structures.	RESULTS
+177	181	KdpE	protein	In this context, the dimer of full-length KdpE from E. coli (Z-score 18.8, rmsd 1.9 Å over 117 Cα atoms) (PDB code: 4KNY) and the structure of the functional dimer of the RD of KdpE from E. coli (PDB code: 1ZH2) represent the most structurally related structures.	RESULTS
+187	194	E. coli	species	In this context, the dimer of full-length KdpE from E. coli (Z-score 18.8, rmsd 1.9 Å over 117 Cα atoms) (PDB code: 4KNY) and the structure of the functional dimer of the RD of KdpE from E. coli (PDB code: 1ZH2) represent the most structurally related structures.	RESULTS
+252	262	structures	evidence	In this context, the dimer of full-length KdpE from E. coli (Z-score 18.8, rmsd 1.9 Å over 117 Cα atoms) (PDB code: 4KNY) and the structure of the functional dimer of the RD of KdpE from E. coli (PDB code: 1ZH2) represent the most structurally related structures.	RESULTS
+3	10	aligned	experimental_method	We aligned NsrR-RD on both monomers of the RD of KdpE. Since helix α4 of NsrR-RD is orientated slightly different when compared with other structures of RDs (Fig 2), helix α4 and the N-terminal loop of one monomer were clashing with the second monomer (S2A Fig).	RESULTS
+11	15	NsrR	protein	We aligned NsrR-RD on both monomers of the RD of KdpE. Since helix α4 of NsrR-RD is orientated slightly different when compared with other structures of RDs (Fig 2), helix α4 and the N-terminal loop of one monomer were clashing with the second monomer (S2A Fig).	RESULTS
+16	18	RD	structure_element	We aligned NsrR-RD on both monomers of the RD of KdpE. Since helix α4 of NsrR-RD is orientated slightly different when compared with other structures of RDs (Fig 2), helix α4 and the N-terminal loop of one monomer were clashing with the second monomer (S2A Fig).	RESULTS
+27	35	monomers	oligomeric_state	We aligned NsrR-RD on both monomers of the RD of KdpE. Since helix α4 of NsrR-RD is orientated slightly different when compared with other structures of RDs (Fig 2), helix α4 and the N-terminal loop of one monomer were clashing with the second monomer (S2A Fig).	RESULTS
+43	45	RD	structure_element	We aligned NsrR-RD on both monomers of the RD of KdpE. Since helix α4 of NsrR-RD is orientated slightly different when compared with other structures of RDs (Fig 2), helix α4 and the N-terminal loop of one monomer were clashing with the second monomer (S2A Fig).	RESULTS
+49	53	KdpE	protein	We aligned NsrR-RD on both monomers of the RD of KdpE. Since helix α4 of NsrR-RD is orientated slightly different when compared with other structures of RDs (Fig 2), helix α4 and the N-terminal loop of one monomer were clashing with the second monomer (S2A Fig).	RESULTS
+61	66	helix	structure_element	We aligned NsrR-RD on both monomers of the RD of KdpE. Since helix α4 of NsrR-RD is orientated slightly different when compared with other structures of RDs (Fig 2), helix α4 and the N-terminal loop of one monomer were clashing with the second monomer (S2A Fig).	RESULTS
+67	69	α4	structure_element	We aligned NsrR-RD on both monomers of the RD of KdpE. Since helix α4 of NsrR-RD is orientated slightly different when compared with other structures of RDs (Fig 2), helix α4 and the N-terminal loop of one monomer were clashing with the second monomer (S2A Fig).	RESULTS
+73	77	NsrR	protein	We aligned NsrR-RD on both monomers of the RD of KdpE. Since helix α4 of NsrR-RD is orientated slightly different when compared with other structures of RDs (Fig 2), helix α4 and the N-terminal loop of one monomer were clashing with the second monomer (S2A Fig).	RESULTS
+78	80	RD	structure_element	We aligned NsrR-RD on both monomers of the RD of KdpE. Since helix α4 of NsrR-RD is orientated slightly different when compared with other structures of RDs (Fig 2), helix α4 and the N-terminal loop of one monomer were clashing with the second monomer (S2A Fig).	RESULTS
+139	149	structures	evidence	We aligned NsrR-RD on both monomers of the RD of KdpE. Since helix α4 of NsrR-RD is orientated slightly different when compared with other structures of RDs (Fig 2), helix α4 and the N-terminal loop of one monomer were clashing with the second monomer (S2A Fig).	RESULTS
+153	156	RDs	structure_element	We aligned NsrR-RD on both monomers of the RD of KdpE. Since helix α4 of NsrR-RD is orientated slightly different when compared with other structures of RDs (Fig 2), helix α4 and the N-terminal loop of one monomer were clashing with the second monomer (S2A Fig).	RESULTS
+166	171	helix	structure_element	We aligned NsrR-RD on both monomers of the RD of KdpE. Since helix α4 of NsrR-RD is orientated slightly different when compared with other structures of RDs (Fig 2), helix α4 and the N-terminal loop of one monomer were clashing with the second monomer (S2A Fig).	RESULTS
+172	174	α4	structure_element	We aligned NsrR-RD on both monomers of the RD of KdpE. Since helix α4 of NsrR-RD is orientated slightly different when compared with other structures of RDs (Fig 2), helix α4 and the N-terminal loop of one monomer were clashing with the second monomer (S2A Fig).	RESULTS
+194	198	loop	structure_element	We aligned NsrR-RD on both monomers of the RD of KdpE. Since helix α4 of NsrR-RD is orientated slightly different when compared with other structures of RDs (Fig 2), helix α4 and the N-terminal loop of one monomer were clashing with the second monomer (S2A Fig).	RESULTS
+206	213	monomer	oligomeric_state	We aligned NsrR-RD on both monomers of the RD of KdpE. Since helix α4 of NsrR-RD is orientated slightly different when compared with other structures of RDs (Fig 2), helix α4 and the N-terminal loop of one monomer were clashing with the second monomer (S2A Fig).	RESULTS
+244	251	monomer	oligomeric_state	We aligned NsrR-RD on both monomers of the RD of KdpE. Since helix α4 of NsrR-RD is orientated slightly different when compared with other structures of RDs (Fig 2), helix α4 and the N-terminal loop of one monomer were clashing with the second monomer (S2A Fig).	RESULTS
+11	16	helix	structure_element	Therefore, helix α4 and the N-terminal loop were shifted to the position of KdpE by primarily modifying backbone torsion angles in the region immediately C-terminal to helix α4.	RESULTS
+17	19	α4	structure_element	Therefore, helix α4 and the N-terminal loop were shifted to the position of KdpE by primarily modifying backbone torsion angles in the region immediately C-terminal to helix α4.	RESULTS
+39	43	loop	structure_element	Therefore, helix α4 and the N-terminal loop were shifted to the position of KdpE by primarily modifying backbone torsion angles in the region immediately C-terminal to helix α4.	RESULTS
+76	80	KdpE	protein	Therefore, helix α4 and the N-terminal loop were shifted to the position of KdpE by primarily modifying backbone torsion angles in the region immediately C-terminal to helix α4.	RESULTS
+168	173	helix	structure_element	Therefore, helix α4 and the N-terminal loop were shifted to the position of KdpE by primarily modifying backbone torsion angles in the region immediately C-terminal to helix α4.	RESULTS
+174	176	α4	structure_element	Therefore, helix α4 and the N-terminal loop were shifted to the position of KdpE by primarily modifying backbone torsion angles in the region immediately C-terminal to helix α4.	RESULTS
+12	17	helix	structure_element	Afterwards, helix α4 and the adjacent loops were energy minimized with the MAB force field as implemented in the program Moloc; all other atoms of NsrR-RD were kept fixed.	RESULTS
+18	20	α4	structure_element	Afterwards, helix α4 and the adjacent loops were energy minimized with the MAB force field as implemented in the program Moloc; all other atoms of NsrR-RD were kept fixed.	RESULTS
+38	43	loops	structure_element	Afterwards, helix α4 and the adjacent loops were energy minimized with the MAB force field as implemented in the program Moloc; all other atoms of NsrR-RD were kept fixed.	RESULTS
+49	90	energy minimized with the MAB force field	experimental_method	Afterwards, helix α4 and the adjacent loops were energy minimized with the MAB force field as implemented in the program Moloc; all other atoms of NsrR-RD were kept fixed.	RESULTS
+147	151	NsrR	protein	Afterwards, helix α4 and the adjacent loops were energy minimized with the MAB force field as implemented in the program Moloc; all other atoms of NsrR-RD were kept fixed.	RESULTS
+152	154	RD	structure_element	Afterwards, helix α4 and the adjacent loops were energy minimized with the MAB force field as implemented in the program Moloc; all other atoms of NsrR-RD were kept fixed.	RESULTS
+42	58	energy minimized	protein_state	The result is highlighted in S2B Fig. The energy minimized structure of NsrR-RD was then superimposed on the dimeric structure of KdpE.	RESULTS
+59	68	structure	evidence	The result is highlighted in S2B Fig. The energy minimized structure of NsrR-RD was then superimposed on the dimeric structure of KdpE.	RESULTS
+72	76	NsrR	protein	The result is highlighted in S2B Fig. The energy minimized structure of NsrR-RD was then superimposed on the dimeric structure of KdpE.	RESULTS
+77	79	RD	structure_element	The result is highlighted in S2B Fig. The energy minimized structure of NsrR-RD was then superimposed on the dimeric structure of KdpE.	RESULTS
+89	101	superimposed	experimental_method	The result is highlighted in S2B Fig. The energy minimized structure of NsrR-RD was then superimposed on the dimeric structure of KdpE.	RESULTS
+109	116	dimeric	oligomeric_state	The result is highlighted in S2B Fig. The energy minimized structure of NsrR-RD was then superimposed on the dimeric structure of KdpE.	RESULTS
+117	126	structure	evidence	The result is highlighted in S2B Fig. The energy minimized structure of NsrR-RD was then superimposed on the dimeric structure of KdpE.	RESULTS
+130	134	KdpE	protein	The result is highlighted in S2B Fig. The energy minimized structure of NsrR-RD was then superimposed on the dimeric structure of KdpE.	RESULTS
+24	29	dimer	oligomeric_state	The putative functional dimer of NsrR-RD is depicted in Fig 5.	RESULTS
+33	37	NsrR	protein	The putative functional dimer of NsrR-RD is depicted in Fig 5.	RESULTS
+38	40	RD	structure_element	The putative functional dimer of NsrR-RD is depicted in Fig 5.	RESULTS
+4	21	dimeric interface	site	The dimeric interface is formed by α4-β5-α5 of RD (Fig 5A), as previously observed in other RRs.	RESULTS
+35	43	α4-β5-α5	structure_element	The dimeric interface is formed by α4-β5-α5 of RD (Fig 5A), as previously observed in other RRs.	RESULTS
+47	49	RD	structure_element	The dimeric interface is formed by α4-β5-α5 of RD (Fig 5A), as previously observed in other RRs.	RESULTS
+92	95	RRs	protein_type	The dimeric interface is formed by α4-β5-α5 of RD (Fig 5A), as previously observed in other RRs.	RESULTS
+3	7	KdpE	protein	In KdpE, a network of salt bridges and other electrostatic interactions stabilize the interface within a single monomer as well as between the monomers.	RESULTS
+22	34	salt bridges	bond_interaction	In KdpE, a network of salt bridges and other electrostatic interactions stabilize the interface within a single monomer as well as between the monomers.	RESULTS
+45	71	electrostatic interactions	bond_interaction	In KdpE, a network of salt bridges and other electrostatic interactions stabilize the interface within a single monomer as well as between the monomers.	RESULTS
+86	95	interface	site	In KdpE, a network of salt bridges and other electrostatic interactions stabilize the interface within a single monomer as well as between the monomers.	RESULTS
+112	119	monomer	oligomeric_state	In KdpE, a network of salt bridges and other electrostatic interactions stabilize the interface within a single monomer as well as between the monomers.	RESULTS
+143	151	monomers	oligomeric_state	In KdpE, a network of salt bridges and other electrostatic interactions stabilize the interface within a single monomer as well as between the monomers.	RESULTS
+57	73	highly conserved	protein_state	Majority of these interactions involve residues that are highly conserved within the OmpR/PhoB subfamily of RRs.	RESULTS
+85	104	OmpR/PhoB subfamily	protein_type	Majority of these interactions involve residues that are highly conserved within the OmpR/PhoB subfamily of RRs.	RESULTS
+108	111	RRs	protein_type	Majority of these interactions involve residues that are highly conserved within the OmpR/PhoB subfamily of RRs.	RESULTS
+17	34	dimeric interface	site	In addition, the dimeric interface of KdpE is characterized by hydrophobic patch formed by residues Ile88 (α4), Leu91 (α4), Ala110 (α5), and Val114 (α5).	RESULTS
+38	42	KdpE	protein	In addition, the dimeric interface of KdpE is characterized by hydrophobic patch formed by residues Ile88 (α4), Leu91 (α4), Ala110 (α5), and Val114 (α5).	RESULTS
+63	80	hydrophobic patch	site	In addition, the dimeric interface of KdpE is characterized by hydrophobic patch formed by residues Ile88 (α4), Leu91 (α4), Ala110 (α5), and Val114 (α5).	RESULTS
+100	105	Ile88	residue_name_number	In addition, the dimeric interface of KdpE is characterized by hydrophobic patch formed by residues Ile88 (α4), Leu91 (α4), Ala110 (α5), and Val114 (α5).	RESULTS
+107	109	α4	structure_element	In addition, the dimeric interface of KdpE is characterized by hydrophobic patch formed by residues Ile88 (α4), Leu91 (α4), Ala110 (α5), and Val114 (α5).	RESULTS
+112	117	Leu91	residue_name_number	In addition, the dimeric interface of KdpE is characterized by hydrophobic patch formed by residues Ile88 (α4), Leu91 (α4), Ala110 (α5), and Val114 (α5).	RESULTS
+119	121	α4	structure_element	In addition, the dimeric interface of KdpE is characterized by hydrophobic patch formed by residues Ile88 (α4), Leu91 (α4), Ala110 (α5), and Val114 (α5).	RESULTS
+124	130	Ala110	residue_name_number	In addition, the dimeric interface of KdpE is characterized by hydrophobic patch formed by residues Ile88 (α4), Leu91 (α4), Ala110 (α5), and Val114 (α5).	RESULTS
+132	134	α5	structure_element	In addition, the dimeric interface of KdpE is characterized by hydrophobic patch formed by residues Ile88 (α4), Leu91 (α4), Ala110 (α5), and Val114 (α5).	RESULTS
+141	147	Val114	residue_name_number	In addition, the dimeric interface of KdpE is characterized by hydrophobic patch formed by residues Ile88 (α4), Leu91 (α4), Ala110 (α5), and Val114 (α5).	RESULTS
+149	151	α5	structure_element	In addition, the dimeric interface of KdpE is characterized by hydrophobic patch formed by residues Ile88 (α4), Leu91 (α4), Ala110 (α5), and Val114 (α5).	RESULTS
+57	61	NsrR	protein	Structurally, a similar set of residues is also found in NsrR: Leu94 (α4), Val110 (α5) and Ala113 (α5), respectively (depicted as spheres in Fig 5B), which are conserved to some extent on sequence level (highlighted in yellow; Fig 3).	RESULTS
+63	68	Leu94	residue_name_number	Structurally, a similar set of residues is also found in NsrR: Leu94 (α4), Val110 (α5) and Ala113 (α5), respectively (depicted as spheres in Fig 5B), which are conserved to some extent on sequence level (highlighted in yellow; Fig 3).	RESULTS
+70	72	α4	structure_element	Structurally, a similar set of residues is also found in NsrR: Leu94 (α4), Val110 (α5) and Ala113 (α5), respectively (depicted as spheres in Fig 5B), which are conserved to some extent on sequence level (highlighted in yellow; Fig 3).	RESULTS
+75	81	Val110	residue_name_number	Structurally, a similar set of residues is also found in NsrR: Leu94 (α4), Val110 (α5) and Ala113 (α5), respectively (depicted as spheres in Fig 5B), which are conserved to some extent on sequence level (highlighted in yellow; Fig 3).	RESULTS
+83	85	α5	structure_element	Structurally, a similar set of residues is also found in NsrR: Leu94 (α4), Val110 (α5) and Ala113 (α5), respectively (depicted as spheres in Fig 5B), which are conserved to some extent on sequence level (highlighted in yellow; Fig 3).	RESULTS
+91	97	Ala113	residue_name_number	Structurally, a similar set of residues is also found in NsrR: Leu94 (α4), Val110 (α5) and Ala113 (α5), respectively (depicted as spheres in Fig 5B), which are conserved to some extent on sequence level (highlighted in yellow; Fig 3).	RESULTS
+99	101	α5	structure_element	Structurally, a similar set of residues is also found in NsrR: Leu94 (α4), Val110 (α5) and Ala113 (α5), respectively (depicted as spheres in Fig 5B), which are conserved to some extent on sequence level (highlighted in yellow; Fig 3).	RESULTS
+160	169	conserved	protein_state	Structurally, a similar set of residues is also found in NsrR: Leu94 (α4), Val110 (α5) and Ala113 (α5), respectively (depicted as spheres in Fig 5B), which are conserved to some extent on sequence level (highlighted in yellow; Fig 3).	RESULTS
+11	16	dimer	oligomeric_state	Functional dimer orientation of the RDs of NsrR.	FIG
+36	39	RDs	structure_element	Functional dimer orientation of the RDs of NsrR.	FIG
+43	47	NsrR	protein	Functional dimer orientation of the RDs of NsrR.	FIG
+0	7	Dimeric	oligomeric_state	Dimeric structure of the RD of NsrR aligned to the structure of KdpE (PDB code 1ZH2, not shown).	FIG
+8	17	structure	evidence	Dimeric structure of the RD of NsrR aligned to the structure of KdpE (PDB code 1ZH2, not shown).	FIG
+25	27	RD	structure_element	Dimeric structure of the RD of NsrR aligned to the structure of KdpE (PDB code 1ZH2, not shown).	FIG
+31	35	NsrR	protein	Dimeric structure of the RD of NsrR aligned to the structure of KdpE (PDB code 1ZH2, not shown).	FIG
+51	60	structure	evidence	Dimeric structure of the RD of NsrR aligned to the structure of KdpE (PDB code 1ZH2, not shown).	FIG
+64	68	KdpE	protein	Dimeric structure of the RD of NsrR aligned to the structure of KdpE (PDB code 1ZH2, not shown).	FIG
+12	20	monomers	oligomeric_state	(a) The two monomers of NsrR as functional dimers are represented in a cartoon representation displayed in cyan and yellow colors.	FIG
+24	28	NsrR	protein	(a) The two monomers of NsrR as functional dimers are represented in a cartoon representation displayed in cyan and yellow colors.	FIG
+43	49	dimers	oligomeric_state	(a) The two monomers of NsrR as functional dimers are represented in a cartoon representation displayed in cyan and yellow colors.	FIG
+19	36	dimeric interface	site	(b) Zoom-in of the dimeric interface mediated by α4-β5-α5.	FIG
+49	57	α4-β5-α5	structure_element	(b) Zoom-in of the dimeric interface mediated by α4-β5-α5.	FIG
+4	11	monomer	oligomeric_state	The monomer-monomer interactions are facilitated by hydrophobic residues (displayed as spheres), inter- and intra-domain interactions (displayed as sticks).	FIG
+12	19	monomer	oligomeric_state	The monomer-monomer interactions are facilitated by hydrophobic residues (displayed as spheres), inter- and intra-domain interactions (displayed as sticks).	FIG
+25	51	electrostatic interactions	bond_interaction	Conserved intermolecular electrostatic interactions further stabilize the monomer-monomer interaction of KdpE and are formed between Asp97 (β5) and Arg111 (α5), Asp96 (α4–β5 loop) and Arg118 (α5), and Asp92 (α4) and Arg113 (α5).	RESULTS
+74	81	monomer	oligomeric_state	Conserved intermolecular electrostatic interactions further stabilize the monomer-monomer interaction of KdpE and are formed between Asp97 (β5) and Arg111 (α5), Asp96 (α4–β5 loop) and Arg118 (α5), and Asp92 (α4) and Arg113 (α5).	RESULTS
+82	89	monomer	oligomeric_state	Conserved intermolecular electrostatic interactions further stabilize the monomer-monomer interaction of KdpE and are formed between Asp97 (β5) and Arg111 (α5), Asp96 (α4–β5 loop) and Arg118 (α5), and Asp92 (α4) and Arg113 (α5).	RESULTS
+105	109	KdpE	protein	Conserved intermolecular electrostatic interactions further stabilize the monomer-monomer interaction of KdpE and are formed between Asp97 (β5) and Arg111 (α5), Asp96 (α4–β5 loop) and Arg118 (α5), and Asp92 (α4) and Arg113 (α5).	RESULTS
+133	138	Asp97	residue_name_number	Conserved intermolecular electrostatic interactions further stabilize the monomer-monomer interaction of KdpE and are formed between Asp97 (β5) and Arg111 (α5), Asp96 (α4–β5 loop) and Arg118 (α5), and Asp92 (α4) and Arg113 (α5).	RESULTS
+140	142	β5	structure_element	Conserved intermolecular electrostatic interactions further stabilize the monomer-monomer interaction of KdpE and are formed between Asp97 (β5) and Arg111 (α5), Asp96 (α4–β5 loop) and Arg118 (α5), and Asp92 (α4) and Arg113 (α5).	RESULTS
+148	154	Arg111	residue_name_number	Conserved intermolecular electrostatic interactions further stabilize the monomer-monomer interaction of KdpE and are formed between Asp97 (β5) and Arg111 (α5), Asp96 (α4–β5 loop) and Arg118 (α5), and Asp92 (α4) and Arg113 (α5).	RESULTS
+156	158	α5	structure_element	Conserved intermolecular electrostatic interactions further stabilize the monomer-monomer interaction of KdpE and are formed between Asp97 (β5) and Arg111 (α5), Asp96 (α4–β5 loop) and Arg118 (α5), and Asp92 (α4) and Arg113 (α5).	RESULTS
+161	166	Asp96	residue_name_number	Conserved intermolecular electrostatic interactions further stabilize the monomer-monomer interaction of KdpE and are formed between Asp97 (β5) and Arg111 (α5), Asp96 (α4–β5 loop) and Arg118 (α5), and Asp92 (α4) and Arg113 (α5).	RESULTS
+168	178	α4–β5 loop	structure_element	Conserved intermolecular electrostatic interactions further stabilize the monomer-monomer interaction of KdpE and are formed between Asp97 (β5) and Arg111 (α5), Asp96 (α4–β5 loop) and Arg118 (α5), and Asp92 (α4) and Arg113 (α5).	RESULTS
+184	190	Arg118	residue_name_number	Conserved intermolecular electrostatic interactions further stabilize the monomer-monomer interaction of KdpE and are formed between Asp97 (β5) and Arg111 (α5), Asp96 (α4–β5 loop) and Arg118 (α5), and Asp92 (α4) and Arg113 (α5).	RESULTS
+192	194	α5	structure_element	Conserved intermolecular electrostatic interactions further stabilize the monomer-monomer interaction of KdpE and are formed between Asp97 (β5) and Arg111 (α5), Asp96 (α4–β5 loop) and Arg118 (α5), and Asp92 (α4) and Arg113 (α5).	RESULTS
+201	206	Asp92	residue_name_number	Conserved intermolecular electrostatic interactions further stabilize the monomer-monomer interaction of KdpE and are formed between Asp97 (β5) and Arg111 (α5), Asp96 (α4–β5 loop) and Arg118 (α5), and Asp92 (α4) and Arg113 (α5).	RESULTS
+208	210	α4	structure_element	Conserved intermolecular electrostatic interactions further stabilize the monomer-monomer interaction of KdpE and are formed between Asp97 (β5) and Arg111 (α5), Asp96 (α4–β5 loop) and Arg118 (α5), and Asp92 (α4) and Arg113 (α5).	RESULTS
+216	222	Arg113	residue_name_number	Conserved intermolecular electrostatic interactions further stabilize the monomer-monomer interaction of KdpE and are formed between Asp97 (β5) and Arg111 (α5), Asp96 (α4–β5 loop) and Arg118 (α5), and Asp92 (α4) and Arg113 (α5).	RESULTS
+224	226	α5	structure_element	Conserved intermolecular electrostatic interactions further stabilize the monomer-monomer interaction of KdpE and are formed between Asp97 (β5) and Arg111 (α5), Asp96 (α4–β5 loop) and Arg118 (α5), and Asp92 (α4) and Arg113 (α5).	RESULTS
+57	64	dimeric	oligomeric_state	Some of these interactions can also be identified in the dimeric model of NsrR-RD.	RESULTS
+74	78	NsrR	protein	Some of these interactions can also be identified in the dimeric model of NsrR-RD.	RESULTS
+79	81	RD	structure_element	Some of these interactions can also be identified in the dimeric model of NsrR-RD.	RESULTS
+6	12	Asp100	residue_name_number	Here, Asp100 (β5) and Lys114 (α5) form an interaction within one monomer, and an intermolecular interaction can be observed between Asn95 (α4) of one monomer with Thr116 (α5) of the other monomer (Fig 3, shown in cyan).	RESULTS
+14	16	β5	structure_element	Here, Asp100 (β5) and Lys114 (α5) form an interaction within one monomer, and an intermolecular interaction can be observed between Asn95 (α4) of one monomer with Thr116 (α5) of the other monomer (Fig 3, shown in cyan).	RESULTS
+22	28	Lys114	residue_name_number	Here, Asp100 (β5) and Lys114 (α5) form an interaction within one monomer, and an intermolecular interaction can be observed between Asn95 (α4) of one monomer with Thr116 (α5) of the other monomer (Fig 3, shown in cyan).	RESULTS
+30	32	α5	structure_element	Here, Asp100 (β5) and Lys114 (α5) form an interaction within one monomer, and an intermolecular interaction can be observed between Asn95 (α4) of one monomer with Thr116 (α5) of the other monomer (Fig 3, shown in cyan).	RESULTS
+65	72	monomer	oligomeric_state	Here, Asp100 (β5) and Lys114 (α5) form an interaction within one monomer, and an intermolecular interaction can be observed between Asn95 (α4) of one monomer with Thr116 (α5) of the other monomer (Fig 3, shown in cyan).	RESULTS
+132	137	Asn95	residue_name_number	Here, Asp100 (β5) and Lys114 (α5) form an interaction within one monomer, and an intermolecular interaction can be observed between Asn95 (α4) of one monomer with Thr116 (α5) of the other monomer (Fig 3, shown in cyan).	RESULTS
+139	141	α4	structure_element	Here, Asp100 (β5) and Lys114 (α5) form an interaction within one monomer, and an intermolecular interaction can be observed between Asn95 (α4) of one monomer with Thr116 (α5) of the other monomer (Fig 3, shown in cyan).	RESULTS
+150	157	monomer	oligomeric_state	Here, Asp100 (β5) and Lys114 (α5) form an interaction within one monomer, and an intermolecular interaction can be observed between Asn95 (α4) of one monomer with Thr116 (α5) of the other monomer (Fig 3, shown in cyan).	RESULTS
+163	169	Thr116	residue_name_number	Here, Asp100 (β5) and Lys114 (α5) form an interaction within one monomer, and an intermolecular interaction can be observed between Asn95 (α4) of one monomer with Thr116 (α5) of the other monomer (Fig 3, shown in cyan).	RESULTS
+171	173	α5	structure_element	Here, Asp100 (β5) and Lys114 (α5) form an interaction within one monomer, and an intermolecular interaction can be observed between Asn95 (α4) of one monomer with Thr116 (α5) of the other monomer (Fig 3, shown in cyan).	RESULTS
+188	195	monomer	oligomeric_state	Here, Asp100 (β5) and Lys114 (α5) form an interaction within one monomer, and an intermolecular interaction can be observed between Asn95 (α4) of one monomer with Thr116 (α5) of the other monomer (Fig 3, shown in cyan).	RESULTS
+0	5	Asp99	residue_name_number	Asp99 (α4–β5 loop; Fig 3, shown in cyan) points toward the side chain of Arg121.	RESULTS
+7	17	α4–β5 loop	structure_element	Asp99 (α4–β5 loop; Fig 3, shown in cyan) points toward the side chain of Arg121.	RESULTS
+73	79	Arg121	residue_name_number	Asp99 (α4–β5 loop; Fig 3, shown in cyan) points toward the side chain of Arg121.	RESULTS
+37	41	KdpE	protein	This interaction is also observed in KdpE (Asp96 (α4–β5 loop) and Arg118 (α5)).	RESULTS
+43	48	Asp96	residue_name_number	This interaction is also observed in KdpE (Asp96 (α4–β5 loop) and Arg118 (α5)).	RESULTS
+50	60	α4–β5 loop	structure_element	This interaction is also observed in KdpE (Asp96 (α4–β5 loop) and Arg118 (α5)).	RESULTS
+66	72	Arg118	residue_name_number	This interaction is also observed in KdpE (Asp96 (α4–β5 loop) and Arg118 (α5)).	RESULTS
+74	76	α5	structure_element	This interaction is also observed in KdpE (Asp96 (α4–β5 loop) and Arg118 (α5)).	RESULTS
+3	7	KdpE	protein	In KdpE, Arg111 is additionally stabilized by another intra-molecular salt bridge with Glu107 (α5).	RESULTS
+9	15	Arg111	residue_name_number	In KdpE, Arg111 is additionally stabilized by another intra-molecular salt bridge with Glu107 (α5).	RESULTS
+70	81	salt bridge	bond_interaction	In KdpE, Arg111 is additionally stabilized by another intra-molecular salt bridge with Glu107 (α5).	RESULTS
+87	93	Glu107	residue_name_number	In KdpE, Arg111 is additionally stabilized by another intra-molecular salt bridge with Glu107 (α5).	RESULTS
+95	97	α5	structure_element	In KdpE, Arg111 is additionally stabilized by another intra-molecular salt bridge with Glu107 (α5).	RESULTS
+18	22	NsrR	protein	Interestingly, in NsrR-RD this amino acid corresponds to Val110 (highlighted in yellow in Fig 3).	RESULTS
+23	25	RD	structure_element	Interestingly, in NsrR-RD this amino acid corresponds to Val110 (highlighted in yellow in Fig 3).	RESULTS
+57	63	Val110	residue_name_number	Interestingly, in NsrR-RD this amino acid corresponds to Val110 (highlighted in yellow in Fig 3).	RESULTS
+20	29	alignment	experimental_method	As observed in this alignment, the above-mentioned arginine residue (Arg111 in KdpE) is either an arginine or a lysine residue (Lys114 in NsrR) in all RRs used in the alignment (Fig 3, shown in cyan).	RESULTS
+51	59	arginine	residue_name	As observed in this alignment, the above-mentioned arginine residue (Arg111 in KdpE) is either an arginine or a lysine residue (Lys114 in NsrR) in all RRs used in the alignment (Fig 3, shown in cyan).	RESULTS
+69	75	Arg111	residue_name_number	As observed in this alignment, the above-mentioned arginine residue (Arg111 in KdpE) is either an arginine or a lysine residue (Lys114 in NsrR) in all RRs used in the alignment (Fig 3, shown in cyan).	RESULTS
+79	83	KdpE	protein	As observed in this alignment, the above-mentioned arginine residue (Arg111 in KdpE) is either an arginine or a lysine residue (Lys114 in NsrR) in all RRs used in the alignment (Fig 3, shown in cyan).	RESULTS
+98	106	arginine	residue_name	As observed in this alignment, the above-mentioned arginine residue (Arg111 in KdpE) is either an arginine or a lysine residue (Lys114 in NsrR) in all RRs used in the alignment (Fig 3, shown in cyan).	RESULTS
+112	118	lysine	residue_name	As observed in this alignment, the above-mentioned arginine residue (Arg111 in KdpE) is either an arginine or a lysine residue (Lys114 in NsrR) in all RRs used in the alignment (Fig 3, shown in cyan).	RESULTS
+128	134	Lys114	residue_name_number	As observed in this alignment, the above-mentioned arginine residue (Arg111 in KdpE) is either an arginine or a lysine residue (Lys114 in NsrR) in all RRs used in the alignment (Fig 3, shown in cyan).	RESULTS
+138	142	NsrR	protein	As observed in this alignment, the above-mentioned arginine residue (Arg111 in KdpE) is either an arginine or a lysine residue (Lys114 in NsrR) in all RRs used in the alignment (Fig 3, shown in cyan).	RESULTS
+151	154	RRs	protein_type	As observed in this alignment, the above-mentioned arginine residue (Arg111 in KdpE) is either an arginine or a lysine residue (Lys114 in NsrR) in all RRs used in the alignment (Fig 3, shown in cyan).	RESULTS
+167	176	alignment	experimental_method	As observed in this alignment, the above-mentioned arginine residue (Arg111 in KdpE) is either an arginine or a lysine residue (Lys114 in NsrR) in all RRs used in the alignment (Fig 3, shown in cyan).	RESULTS
+27	35	arginine	residue_name	Interestingly, whenever an arginine is present at this position (Arg111 in KdpE), a glutamate (Glu107 in KdpE) is present as well, presumably stabilizing the arginine side chain.	RESULTS
+65	71	Arg111	residue_name_number	Interestingly, whenever an arginine is present at this position (Arg111 in KdpE), a glutamate (Glu107 in KdpE) is present as well, presumably stabilizing the arginine side chain.	RESULTS
+75	79	KdpE	protein	Interestingly, whenever an arginine is present at this position (Arg111 in KdpE), a glutamate (Glu107 in KdpE) is present as well, presumably stabilizing the arginine side chain.	RESULTS
+84	93	glutamate	residue_name	Interestingly, whenever an arginine is present at this position (Arg111 in KdpE), a glutamate (Glu107 in KdpE) is present as well, presumably stabilizing the arginine side chain.	RESULTS
+95	101	Glu107	residue_name_number	Interestingly, whenever an arginine is present at this position (Arg111 in KdpE), a glutamate (Glu107 in KdpE) is present as well, presumably stabilizing the arginine side chain.	RESULTS
+105	109	KdpE	protein	Interestingly, whenever an arginine is present at this position (Arg111 in KdpE), a glutamate (Glu107 in KdpE) is present as well, presumably stabilizing the arginine side chain.	RESULTS
+158	166	arginine	residue_name	Interestingly, whenever an arginine is present at this position (Arg111 in KdpE), a glutamate (Glu107 in KdpE) is present as well, presumably stabilizing the arginine side chain.	RESULTS
+16	22	lysine	residue_name	However, when a lysine is present at this position, the glutamate is exchanged to a hydrophobic residue contributing to the hydrophobic patch described above.	RESULTS
+56	65	glutamate	residue_name	However, when a lysine is present at this position, the glutamate is exchanged to a hydrophobic residue contributing to the hydrophobic patch described above.	RESULTS
+124	141	hydrophobic patch	site	However, when a lysine is present at this position, the glutamate is exchanged to a hydrophobic residue contributing to the hydrophobic patch described above.	RESULTS
+36	40	PhoB	protein	Additionally, it has been shown for PhoB from E. coli and PhoP from B. subtilis that mutating the corresponding residues involved in dimerisation (residues Asp100, Val110 and Lys114 in NsrR) results in monomeric form of response regulator which has lost the ability to dimerize as well as display reduced DNA binding capabilities.	RESULTS
+46	53	E. coli	species	Additionally, it has been shown for PhoB from E. coli and PhoP from B. subtilis that mutating the corresponding residues involved in dimerisation (residues Asp100, Val110 and Lys114 in NsrR) results in monomeric form of response regulator which has lost the ability to dimerize as well as display reduced DNA binding capabilities.	RESULTS
+58	62	PhoP	protein	Additionally, it has been shown for PhoB from E. coli and PhoP from B. subtilis that mutating the corresponding residues involved in dimerisation (residues Asp100, Val110 and Lys114 in NsrR) results in monomeric form of response regulator which has lost the ability to dimerize as well as display reduced DNA binding capabilities.	RESULTS
+68	79	B. subtilis	species	Additionally, it has been shown for PhoB from E. coli and PhoP from B. subtilis that mutating the corresponding residues involved in dimerisation (residues Asp100, Val110 and Lys114 in NsrR) results in monomeric form of response regulator which has lost the ability to dimerize as well as display reduced DNA binding capabilities.	RESULTS
+85	93	mutating	experimental_method	Additionally, it has been shown for PhoB from E. coli and PhoP from B. subtilis that mutating the corresponding residues involved in dimerisation (residues Asp100, Val110 and Lys114 in NsrR) results in monomeric form of response regulator which has lost the ability to dimerize as well as display reduced DNA binding capabilities.	RESULTS
+156	162	Asp100	residue_name_number	Additionally, it has been shown for PhoB from E. coli and PhoP from B. subtilis that mutating the corresponding residues involved in dimerisation (residues Asp100, Val110 and Lys114 in NsrR) results in monomeric form of response regulator which has lost the ability to dimerize as well as display reduced DNA binding capabilities.	RESULTS
+164	170	Val110	residue_name_number	Additionally, it has been shown for PhoB from E. coli and PhoP from B. subtilis that mutating the corresponding residues involved in dimerisation (residues Asp100, Val110 and Lys114 in NsrR) results in monomeric form of response regulator which has lost the ability to dimerize as well as display reduced DNA binding capabilities.	RESULTS
+175	181	Lys114	residue_name_number	Additionally, it has been shown for PhoB from E. coli and PhoP from B. subtilis that mutating the corresponding residues involved in dimerisation (residues Asp100, Val110 and Lys114 in NsrR) results in monomeric form of response regulator which has lost the ability to dimerize as well as display reduced DNA binding capabilities.	RESULTS
+185	189	NsrR	protein	Additionally, it has been shown for PhoB from E. coli and PhoP from B. subtilis that mutating the corresponding residues involved in dimerisation (residues Asp100, Val110 and Lys114 in NsrR) results in monomeric form of response regulator which has lost the ability to dimerize as well as display reduced DNA binding capabilities.	RESULTS
+202	211	monomeric	oligomeric_state	Additionally, it has been shown for PhoB from E. coli and PhoP from B. subtilis that mutating the corresponding residues involved in dimerisation (residues Asp100, Val110 and Lys114 in NsrR) results in monomeric form of response regulator which has lost the ability to dimerize as well as display reduced DNA binding capabilities.	RESULTS
+220	238	response regulator	protein_type	Additionally, it has been shown for PhoB from E. coli and PhoP from B. subtilis that mutating the corresponding residues involved in dimerisation (residues Asp100, Val110 and Lys114 in NsrR) results in monomeric form of response regulator which has lost the ability to dimerize as well as display reduced DNA binding capabilities.	RESULTS
+249	277	lost the ability to dimerize	protein_state	Additionally, it has been shown for PhoB from E. coli and PhoP from B. subtilis that mutating the corresponding residues involved in dimerisation (residues Asp100, Val110 and Lys114 in NsrR) results in monomeric form of response regulator which has lost the ability to dimerize as well as display reduced DNA binding capabilities.	RESULTS
+305	308	DNA	chemical	Additionally, it has been shown for PhoB from E. coli and PhoP from B. subtilis that mutating the corresponding residues involved in dimerisation (residues Asp100, Val110 and Lys114 in NsrR) results in monomeric form of response regulator which has lost the ability to dimerize as well as display reduced DNA binding capabilities.	RESULTS
+8	17	Structure	evidence	Overall Structure of C-terminal DNA-binding effector domain of NsrR	RESULTS
+32	59	DNA-binding effector domain	structure_element	Overall Structure of C-terminal DNA-binding effector domain of NsrR	RESULTS
+63	67	NsrR	protein	Overall Structure of C-terminal DNA-binding effector domain of NsrR	RESULTS
+4	13	structure	evidence	The structure of NsrR-ED from S. agalactiae was determined using experimental phases from a single-wavelength anomalous dispersion dataset from the rectangular plate-shaped crystal derivatized with platinum at a resolution of 1.6 Å in space group P21212.	RESULTS
+17	21	NsrR	protein	The structure of NsrR-ED from S. agalactiae was determined using experimental phases from a single-wavelength anomalous dispersion dataset from the rectangular plate-shaped crystal derivatized with platinum at a resolution of 1.6 Å in space group P21212.	RESULTS
+22	24	ED	structure_element	The structure of NsrR-ED from S. agalactiae was determined using experimental phases from a single-wavelength anomalous dispersion dataset from the rectangular plate-shaped crystal derivatized with platinum at a resolution of 1.6 Å in space group P21212.	RESULTS
+30	43	S. agalactiae	species	The structure of NsrR-ED from S. agalactiae was determined using experimental phases from a single-wavelength anomalous dispersion dataset from the rectangular plate-shaped crystal derivatized with platinum at a resolution of 1.6 Å in space group P21212.	RESULTS
+92	138	single-wavelength anomalous dispersion dataset	experimental_method	The structure of NsrR-ED from S. agalactiae was determined using experimental phases from a single-wavelength anomalous dispersion dataset from the rectangular plate-shaped crystal derivatized with platinum at a resolution of 1.6 Å in space group P21212.	RESULTS
+198	206	platinum	chemical	The structure of NsrR-ED from S. agalactiae was determined using experimental phases from a single-wavelength anomalous dispersion dataset from the rectangular plate-shaped crystal derivatized with platinum at a resolution of 1.6 Å in space group P21212.	RESULTS
+4	9	Rwork	evidence	The Rwork and Rfree values after refinement were 0.18 and 0.22, respectively.	RESULTS
+14	19	Rfree	evidence	The Rwork and Rfree values after refinement were 0.18 and 0.22, respectively.	RESULTS
+0	23	Ramachandran validation	evidence	Ramachandran validation was done using MolProbity.	RESULTS
+14	20	Glu128	residue_name_number	The latter is Glu128 (last residue of the linker region) of chain B that is involved in crystal contacts and, therefore, likely adopts an unfavorable conformation.	RESULTS
+42	55	linker region	structure_element	The latter is Glu128 (last residue of the linker region) of chain B that is involved in crystal contacts and, therefore, likely adopts an unfavorable conformation.	RESULTS
+60	67	chain B	structure_element	The latter is Glu128 (last residue of the linker region) of chain B that is involved in crystal contacts and, therefore, likely adopts an unfavorable conformation.	RESULTS
+4	13	structure	evidence	The structure contained a few ethylene glycol molecules introduced by the cryo-protecting procedure.	RESULTS
+30	45	ethylene glycol	chemical	The structure contained a few ethylene glycol molecules introduced by the cryo-protecting procedure.	RESULTS
+15	42	effector DNA-binding domain	structure_element	The C-terminal effector DNA-binding domain of NsrR is about 13 kDa in size and consists of residues 129–243 (including 21 amino acid residues of the expression tag).	RESULTS
+46	50	NsrR	protein	The C-terminal effector DNA-binding domain of NsrR is about 13 kDa in size and consists of residues 129–243 (including 21 amino acid residues of the expression tag).	RESULTS
+100	107	129–243	residue_range	The C-terminal effector DNA-binding domain of NsrR is about 13 kDa in size and consists of residues 129–243 (including 21 amino acid residues of the expression tag).	RESULTS
+0	7	Monomer	oligomeric_state	Monomer A contains residue 129–224 and monomer B contain residues 128–225.	RESULTS
+8	9	A	structure_element	Monomer A contains residue 129–224 and monomer B contain residues 128–225.	RESULTS
+27	34	129–224	residue_range	Monomer A contains residue 129–224 and monomer B contain residues 128–225.	RESULTS
+39	46	monomer	oligomeric_state	Monomer A contains residue 129–224 and monomer B contain residues 128–225.	RESULTS
+47	48	B	structure_element	Monomer A contains residue 129–224 and monomer B contain residues 128–225.	RESULTS
+66	73	128–225	residue_range	Monomer A contains residue 129–224 and monomer B contain residues 128–225.	RESULTS
+4	10	Asp147	residue_name_number	For Asp147 of chain A and Glu174 of chain B, poor electron density was observed for the side chains and, thus, these side chains were removed during refinement.	RESULTS
+14	21	chain A	structure_element	For Asp147 of chain A and Glu174 of chain B, poor electron density was observed for the side chains and, thus, these side chains were removed during refinement.	RESULTS
+26	32	Glu174	residue_name_number	For Asp147 of chain A and Glu174 of chain B, poor electron density was observed for the side chains and, thus, these side chains were removed during refinement.	RESULTS
+36	43	chain B	structure_element	For Asp147 of chain A and Glu174 of chain B, poor electron density was observed for the side chains and, thus, these side chains were removed during refinement.	RESULTS
+50	66	electron density	evidence	For Asp147 of chain A and Glu174 of chain B, poor electron density was observed for the side chains and, thus, these side chains were removed during refinement.	RESULTS
+43	47	NsrR	protein	The asymmetric unit contains two copies of NsrR-ED related by two-fold rotational symmetry.	RESULTS
+48	50	ED	structure_element	The asymmetric unit contains two copies of NsrR-ED related by two-fold rotational symmetry.	RESULTS
+3	10	overlay	experimental_method	An overlay revealed that both monomers display high similarity in their overall structure with an rmsd of 0.5 Å over 95 Cα atoms.	RESULTS
+30	38	monomers	oligomeric_state	An overlay revealed that both monomers display high similarity in their overall structure with an rmsd of 0.5 Å over 95 Cα atoms.	RESULTS
+80	89	structure	evidence	An overlay revealed that both monomers display high similarity in their overall structure with an rmsd of 0.5 Å over 95 Cα atoms.	RESULTS
+98	102	rmsd	evidence	An overlay revealed that both monomers display high similarity in their overall structure with an rmsd of 0.5 Å over 95 Cα atoms.	RESULTS
+38	47	structure	evidence	We therefore describe for the overall structure only monomer A.	RESULTS
+53	60	monomer	oligomeric_state	We therefore describe for the overall structure only monomer A.	RESULTS
+61	62	A	structure_element	We therefore describe for the overall structure only monomer A.	RESULTS
+4	6	ED	structure_element	The ED domain of NsrR consists of six β-strands and three α-helices in a β6-β7-β8-β9-α6-α7-α8-β10-β11 topology (the secondary structure elements are counted in continuation of those of the RD).	RESULTS
+17	21	NsrR	protein	The ED domain of NsrR consists of six β-strands and three α-helices in a β6-β7-β8-β9-α6-α7-α8-β10-β11 topology (the secondary structure elements are counted in continuation of those of the RD).	RESULTS
+38	47	β-strands	structure_element	The ED domain of NsrR consists of six β-strands and three α-helices in a β6-β7-β8-β9-α6-α7-α8-β10-β11 topology (the secondary structure elements are counted in continuation of those of the RD).	RESULTS
+58	67	α-helices	structure_element	The ED domain of NsrR consists of six β-strands and three α-helices in a β6-β7-β8-β9-α6-α7-α8-β10-β11 topology (the secondary structure elements are counted in continuation of those of the RD).	RESULTS
+73	101	β6-β7-β8-β9-α6-α7-α8-β10-β11	structure_element	The ED domain of NsrR consists of six β-strands and three α-helices in a β6-β7-β8-β9-α6-α7-α8-β10-β11 topology (the secondary structure elements are counted in continuation of those of the RD).	RESULTS
+189	191	RD	structure_element	The ED domain of NsrR consists of six β-strands and three α-helices in a β6-β7-β8-β9-α6-α7-α8-β10-β11 topology (the secondary structure elements are counted in continuation of those of the RD).	RESULTS
+4	19	effector domain	structure_element	The effector domain starts with a 4-stranded antiparallel β-sheet, followed by three α-helices and eventually ends in a C-terminal β-hairpin (Fig 6).	RESULTS
+34	65	4-stranded antiparallel β-sheet	structure_element	The effector domain starts with a 4-stranded antiparallel β-sheet, followed by three α-helices and eventually ends in a C-terminal β-hairpin (Fig 6).	RESULTS
+85	94	α-helices	structure_element	The effector domain starts with a 4-stranded antiparallel β-sheet, followed by three α-helices and eventually ends in a C-terminal β-hairpin (Fig 6).	RESULTS
+131	140	β-hairpin	structure_element	The effector domain starts with a 4-stranded antiparallel β-sheet, followed by three α-helices and eventually ends in a C-terminal β-hairpin (Fig 6).	RESULTS
+8	16	β-sheets	structure_element	The two β-sheets sandwich the three α-helices.	RESULTS
+36	45	α-helices	structure_element	The two β-sheets sandwich the three α-helices.	RESULTS
+0	9	Structure	evidence	Structure of the C-terminal effector domain of NsrR.	FIG
+28	43	effector domain	structure_element	Structure of the C-terminal effector domain of NsrR.	FIG
+47	51	NsrR	protein	Structure of the C-terminal effector domain of NsrR.	FIG
+41	56	effector domain	structure_element	Cartoon representation of the C-terminal effector domain of NsrR (green; recognition helix in cyan).	FIG
+60	64	NsrR	protein	Cartoon representation of the C-terminal effector domain of NsrR (green; recognition helix in cyan).	FIG
+73	90	recognition helix	structure_element	Cartoon representation of the C-terminal effector domain of NsrR (green; recognition helix in cyan).	FIG
+65	81	effector domains	structure_element	The structural areas with the highest variations compared to the effector domains of DrrB (pink, 1P2F), MtrA (grey, 2GWR), and PhoB (blue, 1GXQ) are marked.	FIG
+85	89	DrrB	protein	The structural areas with the highest variations compared to the effector domains of DrrB (pink, 1P2F), MtrA (grey, 2GWR), and PhoB (blue, 1GXQ) are marked.	FIG
+104	108	MtrA	protein	The structural areas with the highest variations compared to the effector domains of DrrB (pink, 1P2F), MtrA (grey, 2GWR), and PhoB (blue, 1GXQ) are marked.	FIG
+127	131	PhoB	protein	The structural areas with the highest variations compared to the effector domains of DrrB (pink, 1P2F), MtrA (grey, 2GWR), and PhoB (blue, 1GXQ) are marked.	FIG
+4	24	transactivation loop	structure_element	The transactivation loop of MtrA is missing in the structure, therefore, the two termini are connected by a dashed line.	FIG
+28	32	MtrA	protein	The transactivation loop of MtrA is missing in the structure, therefore, the two termini are connected by a dashed line.	FIG
+36	43	missing	protein_state	The transactivation loop of MtrA is missing in the structure, therefore, the two termini are connected by a dashed line.	FIG
+51	60	structure	evidence	The transactivation loop of MtrA is missing in the structure, therefore, the two termini are connected by a dashed line.	FIG
+34	53	OmpR/PhoB subfamily	protein_type	The characteristic feature of the OmpR/PhoB subfamily of RRs is a winged helix-turn-helix (wHTH) fold that is adopted by the α7-loop-α8 segment in full-length and single effector domain structures of RRs of this subfamily.	RESULTS
+57	60	RRs	protein_type	The characteristic feature of the OmpR/PhoB subfamily of RRs is a winged helix-turn-helix (wHTH) fold that is adopted by the α7-loop-α8 segment in full-length and single effector domain structures of RRs of this subfamily.	RESULTS
+66	89	winged helix-turn-helix	structure_element	The characteristic feature of the OmpR/PhoB subfamily of RRs is a winged helix-turn-helix (wHTH) fold that is adopted by the α7-loop-α8 segment in full-length and single effector domain structures of RRs of this subfamily.	RESULTS
+91	95	wHTH	structure_element	The characteristic feature of the OmpR/PhoB subfamily of RRs is a winged helix-turn-helix (wHTH) fold that is adopted by the α7-loop-α8 segment in full-length and single effector domain structures of RRs of this subfamily.	RESULTS
+125	143	α7-loop-α8 segment	structure_element	The characteristic feature of the OmpR/PhoB subfamily of RRs is a winged helix-turn-helix (wHTH) fold that is adopted by the α7-loop-α8 segment in full-length and single effector domain structures of RRs of this subfamily.	RESULTS
+147	158	full-length	protein_state	The characteristic feature of the OmpR/PhoB subfamily of RRs is a winged helix-turn-helix (wHTH) fold that is adopted by the α7-loop-α8 segment in full-length and single effector domain structures of RRs of this subfamily.	RESULTS
+170	185	effector domain	structure_element	The characteristic feature of the OmpR/PhoB subfamily of RRs is a winged helix-turn-helix (wHTH) fold that is adopted by the α7-loop-α8 segment in full-length and single effector domain structures of RRs of this subfamily.	RESULTS
+186	196	structures	evidence	The characteristic feature of the OmpR/PhoB subfamily of RRs is a winged helix-turn-helix (wHTH) fold that is adopted by the α7-loop-α8 segment in full-length and single effector domain structures of RRs of this subfamily.	RESULTS
+200	203	RRs	protein_type	The characteristic feature of the OmpR/PhoB subfamily of RRs is a winged helix-turn-helix (wHTH) fold that is adopted by the α7-loop-α8 segment in full-length and single effector domain structures of RRs of this subfamily.	RESULTS
+4	13	structure	evidence	The structure of NsrR-ED also contains such a wHTH motif built up by helices α7 and α8 (Fig 6).	RESULTS
+17	21	NsrR	protein	The structure of NsrR-ED also contains such a wHTH motif built up by helices α7 and α8 (Fig 6).	RESULTS
+22	24	ED	structure_element	The structure of NsrR-ED also contains such a wHTH motif built up by helices α7 and α8 (Fig 6).	RESULTS
+46	50	wHTH	structure_element	The structure of NsrR-ED also contains such a wHTH motif built up by helices α7 and α8 (Fig 6).	RESULTS
+69	76	helices	structure_element	The structure of NsrR-ED also contains such a wHTH motif built up by helices α7 and α8 (Fig 6).	RESULTS
+77	79	α7	structure_element	The structure of NsrR-ED also contains such a wHTH motif built up by helices α7 and α8 (Fig 6).	RESULTS
+84	86	α8	structure_element	The structure of NsrR-ED also contains such a wHTH motif built up by helices α7 and α8 (Fig 6).	RESULTS
+11	16	helix	structure_element	The second helix of the wHTH motif is important for DNA-binding and, therefore, is termed “recognition helix” (shown in cyan in Fig 6).	RESULTS
+24	28	wHTH	structure_element	The second helix of the wHTH motif is important for DNA-binding and, therefore, is termed “recognition helix” (shown in cyan in Fig 6).	RESULTS
+52	55	DNA	chemical	The second helix of the wHTH motif is important for DNA-binding and, therefore, is termed “recognition helix” (shown in cyan in Fig 6).	RESULTS
+91	108	recognition helix	structure_element	The second helix of the wHTH motif is important for DNA-binding and, therefore, is termed “recognition helix” (shown in cyan in Fig 6).	RESULTS
+15	20	helix	structure_element	Furthermore, a helix within the HTH motif, named “positioning helix”, is important for proper orientation and positioning of the loop between these two helices and is referred to as “transactivation loop” (also called α-loop; Fig 6).	RESULTS
+32	35	HTH	structure_element	Furthermore, a helix within the HTH motif, named “positioning helix”, is important for proper orientation and positioning of the loop between these two helices and is referred to as “transactivation loop” (also called α-loop; Fig 6).	RESULTS
+50	67	positioning helix	structure_element	Furthermore, a helix within the HTH motif, named “positioning helix”, is important for proper orientation and positioning of the loop between these two helices and is referred to as “transactivation loop” (also called α-loop; Fig 6).	RESULTS
+129	133	loop	structure_element	Furthermore, a helix within the HTH motif, named “positioning helix”, is important for proper orientation and positioning of the loop between these two helices and is referred to as “transactivation loop” (also called α-loop; Fig 6).	RESULTS
+183	203	transactivation loop	structure_element	Furthermore, a helix within the HTH motif, named “positioning helix”, is important for proper orientation and positioning of the loop between these two helices and is referred to as “transactivation loop” (also called α-loop; Fig 6).	RESULTS
+218	224	α-loop	structure_element	Furthermore, a helix within the HTH motif, named “positioning helix”, is important for proper orientation and positioning of the loop between these two helices and is referred to as “transactivation loop” (also called α-loop; Fig 6).	RESULTS
+7	16	structure	evidence	In the structure of NsrR-ED, helix α8 is identified as the recognition helix, α7 as the positioning helix, and the loop region between helices α7-α8 as transactivation loop as observed in other RRs (Fig 6).	RESULTS
+20	24	NsrR	protein	In the structure of NsrR-ED, helix α8 is identified as the recognition helix, α7 as the positioning helix, and the loop region between helices α7-α8 as transactivation loop as observed in other RRs (Fig 6).	RESULTS
+25	27	ED	structure_element	In the structure of NsrR-ED, helix α8 is identified as the recognition helix, α7 as the positioning helix, and the loop region between helices α7-α8 as transactivation loop as observed in other RRs (Fig 6).	RESULTS
+29	34	helix	structure_element	In the structure of NsrR-ED, helix α8 is identified as the recognition helix, α7 as the positioning helix, and the loop region between helices α7-α8 as transactivation loop as observed in other RRs (Fig 6).	RESULTS
+35	37	α8	structure_element	In the structure of NsrR-ED, helix α8 is identified as the recognition helix, α7 as the positioning helix, and the loop region between helices α7-α8 as transactivation loop as observed in other RRs (Fig 6).	RESULTS
+59	76	recognition helix	structure_element	In the structure of NsrR-ED, helix α8 is identified as the recognition helix, α7 as the positioning helix, and the loop region between helices α7-α8 as transactivation loop as observed in other RRs (Fig 6).	RESULTS
+78	80	α7	structure_element	In the structure of NsrR-ED, helix α8 is identified as the recognition helix, α7 as the positioning helix, and the loop region between helices α7-α8 as transactivation loop as observed in other RRs (Fig 6).	RESULTS
+88	105	positioning helix	structure_element	In the structure of NsrR-ED, helix α8 is identified as the recognition helix, α7 as the positioning helix, and the loop region between helices α7-α8 as transactivation loop as observed in other RRs (Fig 6).	RESULTS
+115	126	loop region	structure_element	In the structure of NsrR-ED, helix α8 is identified as the recognition helix, α7 as the positioning helix, and the loop region between helices α7-α8 as transactivation loop as observed in other RRs (Fig 6).	RESULTS
+143	148	α7-α8	structure_element	In the structure of NsrR-ED, helix α8 is identified as the recognition helix, α7 as the positioning helix, and the loop region between helices α7-α8 as transactivation loop as observed in other RRs (Fig 6).	RESULTS
+152	172	transactivation loop	structure_element	In the structure of NsrR-ED, helix α8 is identified as the recognition helix, α7 as the positioning helix, and the loop region between helices α7-α8 as transactivation loop as observed in other RRs (Fig 6).	RESULTS
+194	197	RRs	protein_type	In the structure of NsrR-ED, helix α8 is identified as the recognition helix, α7 as the positioning helix, and the loop region between helices α7-α8 as transactivation loop as observed in other RRs (Fig 6).	RESULTS
+21	36	solvent-exposed	protein_state	The 16-residue long, solvent-exposed recognition helix α8 of NsrR-ED contains four positively charged residues that can potentially interact with DNA.	RESULTS
+37	54	recognition helix	structure_element	The 16-residue long, solvent-exposed recognition helix α8 of NsrR-ED contains four positively charged residues that can potentially interact with DNA.	RESULTS
+55	57	α8	structure_element	The 16-residue long, solvent-exposed recognition helix α8 of NsrR-ED contains four positively charged residues that can potentially interact with DNA.	RESULTS
+61	65	NsrR	protein	The 16-residue long, solvent-exposed recognition helix α8 of NsrR-ED contains four positively charged residues that can potentially interact with DNA.	RESULTS
+66	68	ED	structure_element	The 16-residue long, solvent-exposed recognition helix α8 of NsrR-ED contains four positively charged residues that can potentially interact with DNA.	RESULTS
+146	149	DNA	chemical	The 16-residue long, solvent-exposed recognition helix α8 of NsrR-ED contains four positively charged residues that can potentially interact with DNA.	RESULTS
+10	16	Arg198	residue_name_number	These are Arg198, Arg200, Lys201, and Lys202.	RESULTS
+18	24	Arg200	residue_name_number	These are Arg198, Arg200, Lys201, and Lys202.	RESULTS
+26	32	Lys201	residue_name_number	These are Arg198, Arg200, Lys201, and Lys202.	RESULTS
+38	44	Lys202	residue_name_number	These are Arg198, Arg200, Lys201, and Lys202.	RESULTS
+31	35	NsrR	protein	When comparing the sequence of NsrR with PhoB, KdpE, and MtrA, the alignment (Fig 3, colored in blue) emphasizes the variations at these positions, except for Arg200, which is conserved throughout the lantibiotic resistance RRs.	RESULTS
+41	45	PhoB	protein	When comparing the sequence of NsrR with PhoB, KdpE, and MtrA, the alignment (Fig 3, colored in blue) emphasizes the variations at these positions, except for Arg200, which is conserved throughout the lantibiotic resistance RRs.	RESULTS
+47	51	KdpE	protein	When comparing the sequence of NsrR with PhoB, KdpE, and MtrA, the alignment (Fig 3, colored in blue) emphasizes the variations at these positions, except for Arg200, which is conserved throughout the lantibiotic resistance RRs.	RESULTS
+57	61	MtrA	protein	When comparing the sequence of NsrR with PhoB, KdpE, and MtrA, the alignment (Fig 3, colored in blue) emphasizes the variations at these positions, except for Arg200, which is conserved throughout the lantibiotic resistance RRs.	RESULTS
+67	76	alignment	experimental_method	When comparing the sequence of NsrR with PhoB, KdpE, and MtrA, the alignment (Fig 3, colored in blue) emphasizes the variations at these positions, except for Arg200, which is conserved throughout the lantibiotic resistance RRs.	RESULTS
+159	165	Arg200	residue_name_number	When comparing the sequence of NsrR with PhoB, KdpE, and MtrA, the alignment (Fig 3, colored in blue) emphasizes the variations at these positions, except for Arg200, which is conserved throughout the lantibiotic resistance RRs.	RESULTS
+176	185	conserved	protein_state	When comparing the sequence of NsrR with PhoB, KdpE, and MtrA, the alignment (Fig 3, colored in blue) emphasizes the variations at these positions, except for Arg200, which is conserved throughout the lantibiotic resistance RRs.	RESULTS
+201	227	lantibiotic resistance RRs	protein_type	When comparing the sequence of NsrR with PhoB, KdpE, and MtrA, the alignment (Fig 3, colored in blue) emphasizes the variations at these positions, except for Arg200, which is conserved throughout the lantibiotic resistance RRs.	RESULTS
+14	20	Lys202	residue_name_number	Additionally, Lys202 is also highly conserved throughout the family of RRs except PhoB, clearly reflecting differences in the sequences of DNA to be bound.	RESULTS
+29	45	highly conserved	protein_state	Additionally, Lys202 is also highly conserved throughout the family of RRs except PhoB, clearly reflecting differences in the sequences of DNA to be bound.	RESULTS
+71	74	RRs	protein_type	Additionally, Lys202 is also highly conserved throughout the family of RRs except PhoB, clearly reflecting differences in the sequences of DNA to be bound.	RESULTS
+82	86	PhoB	protein	Additionally, Lys202 is also highly conserved throughout the family of RRs except PhoB, clearly reflecting differences in the sequences of DNA to be bound.	RESULTS
+139	142	DNA	chemical	Additionally, Lys202 is also highly conserved throughout the family of RRs except PhoB, clearly reflecting differences in the sequences of DNA to be bound.	RESULTS
+16	26	structures	evidence	Comparison with structures of other effector domains	RESULTS
+36	52	effector domains	structure_element	Comparison with structures of other effector domains	RESULTS
+15	26	DALI search	experimental_method	We performed a DALI search to identify structurally related proteins to NsrR-ED.	RESULTS
+72	76	NsrR	protein	We performed a DALI search to identify structurally related proteins to NsrR-ED.	RESULTS
+77	79	ED	structure_element	We performed a DALI search to identify structurally related proteins to NsrR-ED.	RESULTS
+9	18	structure	evidence	Here the structure of the effector domain of PhoB from E. coli (PDB code: 1GXQ) (Z-score of 13.7) is structurally the most closely related.	RESULTS
+26	41	effector domain	structure_element	Here the structure of the effector domain of PhoB from E. coli (PDB code: 1GXQ) (Z-score of 13.7) is structurally the most closely related.	RESULTS
+45	49	PhoB	protein	Here the structure of the effector domain of PhoB from E. coli (PDB code: 1GXQ) (Z-score of 13.7) is structurally the most closely related.	RESULTS
+55	62	E. coli	species	Here the structure of the effector domain of PhoB from E. coli (PDB code: 1GXQ) (Z-score of 13.7) is structurally the most closely related.	RESULTS
+81	88	Z-score	evidence	Here the structure of the effector domain of PhoB from E. coli (PDB code: 1GXQ) (Z-score of 13.7) is structurally the most closely related.	RESULTS
+15	19	PhoB	protein	Similar to the PhoB effector domain, a 9-residues long loop (amino acid 182–189) is also present in the structure of NsrR-ED that connects helices α7 and α8.	RESULTS
+20	35	effector domain	structure_element	Similar to the PhoB effector domain, a 9-residues long loop (amino acid 182–189) is also present in the structure of NsrR-ED that connects helices α7 and α8.	RESULTS
+55	59	loop	structure_element	Similar to the PhoB effector domain, a 9-residues long loop (amino acid 182–189) is also present in the structure of NsrR-ED that connects helices α7 and α8.	RESULTS
+72	79	182–189	residue_range	Similar to the PhoB effector domain, a 9-residues long loop (amino acid 182–189) is also present in the structure of NsrR-ED that connects helices α7 and α8.	RESULTS
+104	113	structure	evidence	Similar to the PhoB effector domain, a 9-residues long loop (amino acid 182–189) is also present in the structure of NsrR-ED that connects helices α7 and α8.	RESULTS
+117	121	NsrR	protein	Similar to the PhoB effector domain, a 9-residues long loop (amino acid 182–189) is also present in the structure of NsrR-ED that connects helices α7 and α8.	RESULTS
+122	124	ED	structure_element	Similar to the PhoB effector domain, a 9-residues long loop (amino acid 182–189) is also present in the structure of NsrR-ED that connects helices α7 and α8.	RESULTS
+139	146	helices	structure_element	Similar to the PhoB effector domain, a 9-residues long loop (amino acid 182–189) is also present in the structure of NsrR-ED that connects helices α7 and α8.	RESULTS
+147	149	α7	structure_element	Similar to the PhoB effector domain, a 9-residues long loop (amino acid 182–189) is also present in the structure of NsrR-ED that connects helices α7 and α8.	RESULTS
+154	156	α8	structure_element	Similar to the PhoB effector domain, a 9-residues long loop (amino acid 182–189) is also present in the structure of NsrR-ED that connects helices α7 and α8.	RESULTS
+4	8	rmsd	evidence	The rmsd between the three helices of the effector domain (including the two helices forming the wHTH motif) of PhoB and NsrR-ED is 1.6 Å over 47 Cα atoms, clearly indicating that NsrR belongs to the OmpR/PhoB family of RRs.	RESULTS
+42	57	effector domain	structure_element	The rmsd between the three helices of the effector domain (including the two helices forming the wHTH motif) of PhoB and NsrR-ED is 1.6 Å over 47 Cα atoms, clearly indicating that NsrR belongs to the OmpR/PhoB family of RRs.	RESULTS
+77	84	helices	structure_element	The rmsd between the three helices of the effector domain (including the two helices forming the wHTH motif) of PhoB and NsrR-ED is 1.6 Å over 47 Cα atoms, clearly indicating that NsrR belongs to the OmpR/PhoB family of RRs.	RESULTS
+97	101	wHTH	structure_element	The rmsd between the three helices of the effector domain (including the two helices forming the wHTH motif) of PhoB and NsrR-ED is 1.6 Å over 47 Cα atoms, clearly indicating that NsrR belongs to the OmpR/PhoB family of RRs.	RESULTS
+112	116	PhoB	protein	The rmsd between the three helices of the effector domain (including the two helices forming the wHTH motif) of PhoB and NsrR-ED is 1.6 Å over 47 Cα atoms, clearly indicating that NsrR belongs to the OmpR/PhoB family of RRs.	RESULTS
+121	125	NsrR	protein	The rmsd between the three helices of the effector domain (including the two helices forming the wHTH motif) of PhoB and NsrR-ED is 1.6 Å over 47 Cα atoms, clearly indicating that NsrR belongs to the OmpR/PhoB family of RRs.	RESULTS
+126	128	ED	structure_element	The rmsd between the three helices of the effector domain (including the two helices forming the wHTH motif) of PhoB and NsrR-ED is 1.6 Å over 47 Cα atoms, clearly indicating that NsrR belongs to the OmpR/PhoB family of RRs.	RESULTS
+180	184	NsrR	protein	The rmsd between the three helices of the effector domain (including the two helices forming the wHTH motif) of PhoB and NsrR-ED is 1.6 Å over 47 Cα atoms, clearly indicating that NsrR belongs to the OmpR/PhoB family of RRs.	RESULTS
+200	223	OmpR/PhoB family of RRs	protein_type	The rmsd between the three helices of the effector domain (including the two helices forming the wHTH motif) of PhoB and NsrR-ED is 1.6 Å over 47 Cα atoms, clearly indicating that NsrR belongs to the OmpR/PhoB family of RRs.	RESULTS
+14	26	superimposed	experimental_method	Therefore, we superimposed the Cα traces of the effector domain of NsrR (NsrR-ED) with other previously determined effector domains from the OmpR/PhoB family such as DrrB, MtrA and of only the effector domain structure of PhoB from E. coli.	RESULTS
+48	63	effector domain	structure_element	Therefore, we superimposed the Cα traces of the effector domain of NsrR (NsrR-ED) with other previously determined effector domains from the OmpR/PhoB family such as DrrB, MtrA and of only the effector domain structure of PhoB from E. coli.	RESULTS
+67	71	NsrR	protein	Therefore, we superimposed the Cα traces of the effector domain of NsrR (NsrR-ED) with other previously determined effector domains from the OmpR/PhoB family such as DrrB, MtrA and of only the effector domain structure of PhoB from E. coli.	RESULTS
+73	77	NsrR	protein	Therefore, we superimposed the Cα traces of the effector domain of NsrR (NsrR-ED) with other previously determined effector domains from the OmpR/PhoB family such as DrrB, MtrA and of only the effector domain structure of PhoB from E. coli.	RESULTS
+78	80	ED	structure_element	Therefore, we superimposed the Cα traces of the effector domain of NsrR (NsrR-ED) with other previously determined effector domains from the OmpR/PhoB family such as DrrB, MtrA and of only the effector domain structure of PhoB from E. coli.	RESULTS
+115	131	effector domains	structure_element	Therefore, we superimposed the Cα traces of the effector domain of NsrR (NsrR-ED) with other previously determined effector domains from the OmpR/PhoB family such as DrrB, MtrA and of only the effector domain structure of PhoB from E. coli.	RESULTS
+141	157	OmpR/PhoB family	protein_type	Therefore, we superimposed the Cα traces of the effector domain of NsrR (NsrR-ED) with other previously determined effector domains from the OmpR/PhoB family such as DrrB, MtrA and of only the effector domain structure of PhoB from E. coli.	RESULTS
+166	170	DrrB	protein	Therefore, we superimposed the Cα traces of the effector domain of NsrR (NsrR-ED) with other previously determined effector domains from the OmpR/PhoB family such as DrrB, MtrA and of only the effector domain structure of PhoB from E. coli.	RESULTS
+172	176	MtrA	protein	Therefore, we superimposed the Cα traces of the effector domain of NsrR (NsrR-ED) with other previously determined effector domains from the OmpR/PhoB family such as DrrB, MtrA and of only the effector domain structure of PhoB from E. coli.	RESULTS
+193	208	effector domain	structure_element	Therefore, we superimposed the Cα traces of the effector domain of NsrR (NsrR-ED) with other previously determined effector domains from the OmpR/PhoB family such as DrrB, MtrA and of only the effector domain structure of PhoB from E. coli.	RESULTS
+209	218	structure	evidence	Therefore, we superimposed the Cα traces of the effector domain of NsrR (NsrR-ED) with other previously determined effector domains from the OmpR/PhoB family such as DrrB, MtrA and of only the effector domain structure of PhoB from E. coli.	RESULTS
+222	226	PhoB	protein	Therefore, we superimposed the Cα traces of the effector domain of NsrR (NsrR-ED) with other previously determined effector domains from the OmpR/PhoB family such as DrrB, MtrA and of only the effector domain structure of PhoB from E. coli.	RESULTS
+232	239	E. coli	species	Therefore, we superimposed the Cα traces of the effector domain of NsrR (NsrR-ED) with other previously determined effector domains from the OmpR/PhoB family such as DrrB, MtrA and of only the effector domain structure of PhoB from E. coli.	RESULTS
+13	23	structures	evidence	Overall, the structures are very similar with rmsd’s ranging from 1.7 to 2.6 Å (Table 2).	RESULTS
+46	50	rmsd	evidence	Overall, the structures are very similar with rmsd’s ranging from 1.7 to 2.6 Å (Table 2).	RESULTS
+53	57	loop	structure_element	The highest variations (Fig 6) are visible in in the loop regions α7-α8, which corresponds to the transactivation loop.	RESULTS
+66	71	α7-α8	structure_element	The highest variations (Fig 6) are visible in in the loop regions α7-α8, which corresponds to the transactivation loop.	RESULTS
+98	118	transactivation loop	structure_element	The highest variations (Fig 6) are visible in in the loop regions α7-α8, which corresponds to the transactivation loop.	RESULTS
+8	11	RRs	protein_type	In many RRs this transactivation loop along with the recognition helix α8, form inter-domain contacts in the inactive state and are only exposed upon activation of the RRs via a conformational change where the N- and C-terminal domains move away from each other.	RESULTS
+17	37	transactivation loop	structure_element	In many RRs this transactivation loop along with the recognition helix α8, form inter-domain contacts in the inactive state and are only exposed upon activation of the RRs via a conformational change where the N- and C-terminal domains move away from each other.	RESULTS
+53	70	recognition helix	structure_element	In many RRs this transactivation loop along with the recognition helix α8, form inter-domain contacts in the inactive state and are only exposed upon activation of the RRs via a conformational change where the N- and C-terminal domains move away from each other.	RESULTS
+71	73	α8	structure_element	In many RRs this transactivation loop along with the recognition helix α8, form inter-domain contacts in the inactive state and are only exposed upon activation of the RRs via a conformational change where the N- and C-terminal domains move away from each other.	RESULTS
+109	117	inactive	protein_state	In many RRs this transactivation loop along with the recognition helix α8, form inter-domain contacts in the inactive state and are only exposed upon activation of the RRs via a conformational change where the N- and C-terminal domains move away from each other.	RESULTS
+168	171	RRs	protein_type	In many RRs this transactivation loop along with the recognition helix α8, form inter-domain contacts in the inactive state and are only exposed upon activation of the RRs via a conformational change where the N- and C-terminal domains move away from each other.	RESULTS
+0	13	Linker region	structure_element	Linker region	RESULTS
+4	11	linkers	structure_element	The linkers that connect the RDs and EDs in response regulators are highly variable with respect to both length and sequence.	RESULTS
+29	32	RDs	structure_element	The linkers that connect the RDs and EDs in response regulators are highly variable with respect to both length and sequence.	RESULTS
+37	40	EDs	structure_element	The linkers that connect the RDs and EDs in response regulators are highly variable with respect to both length and sequence.	RESULTS
+44	63	response regulators	protein_type	The linkers that connect the RDs and EDs in response regulators are highly variable with respect to both length and sequence.	RESULTS
+68	83	highly variable	protein_state	The linkers that connect the RDs and EDs in response regulators are highly variable with respect to both length and sequence.	RESULTS
+30	37	linkers	structure_element	The exact boundaries of these linkers are difficult to predict from sequence alignments in the absence of structural information of the distinct RR.	RESULTS
+68	87	sequence alignments	experimental_method	The exact boundaries of these linkers are difficult to predict from sequence alignments in the absence of structural information of the distinct RR.	RESULTS
+95	105	absence of	protein_state	The exact boundaries of these linkers are difficult to predict from sequence alignments in the absence of structural information of the distinct RR.	RESULTS
+145	147	RR	protein_type	The exact boundaries of these linkers are difficult to predict from sequence alignments in the absence of structural information of the distinct RR.	RESULTS
+0	6	Linker	structure_element	Linker lengths in OmpR/PhoB proteins of unknown structure have been estimated by comparing the number of residues between conserved landmark residues in the regulatory and effector domains to those from structurally characterized family members.	RESULTS
+18	36	OmpR/PhoB proteins	protein_type	Linker lengths in OmpR/PhoB proteins of unknown structure have been estimated by comparing the number of residues between conserved landmark residues in the regulatory and effector domains to those from structurally characterized family members.	RESULTS
+157	188	regulatory and effector domains	structure_element	Linker lengths in OmpR/PhoB proteins of unknown structure have been estimated by comparing the number of residues between conserved landmark residues in the regulatory and effector domains to those from structurally characterized family members.	RESULTS
+15	31	OmpR/PhoB family	protein_type	Similar to the OmpR/PhoB family, the lantibiotic resistance-associated family of response regulators also displays diverse linker regions, which are recognized in sequence alignments by the introduction of gaps (Fig 3).	RESULTS
+37	100	lantibiotic resistance-associated family of response regulators	protein_type	Similar to the OmpR/PhoB family, the lantibiotic resistance-associated family of response regulators also displays diverse linker regions, which are recognized in sequence alignments by the introduction of gaps (Fig 3).	RESULTS
+123	137	linker regions	structure_element	Similar to the OmpR/PhoB family, the lantibiotic resistance-associated family of response regulators also displays diverse linker regions, which are recognized in sequence alignments by the introduction of gaps (Fig 3).	RESULTS
+163	182	sequence alignments	experimental_method	Similar to the OmpR/PhoB family, the lantibiotic resistance-associated family of response regulators also displays diverse linker regions, which are recognized in sequence alignments by the introduction of gaps (Fig 3).	RESULTS
+19	27	arginine	residue_name	Interestingly, two arginine residues (Arg120 and Arg121 in NsrR; Fig 3, shown in purple) at the end of the RDs seem to be strictly conserved throughout the family of response regulators in both the OmpR/PhoB and lantibiotic resistance-associated RRs, indicating a conserved similarity.	RESULTS
+38	44	Arg120	residue_name_number	Interestingly, two arginine residues (Arg120 and Arg121 in NsrR; Fig 3, shown in purple) at the end of the RDs seem to be strictly conserved throughout the family of response regulators in both the OmpR/PhoB and lantibiotic resistance-associated RRs, indicating a conserved similarity.	RESULTS
+49	55	Arg121	residue_name_number	Interestingly, two arginine residues (Arg120 and Arg121 in NsrR; Fig 3, shown in purple) at the end of the RDs seem to be strictly conserved throughout the family of response regulators in both the OmpR/PhoB and lantibiotic resistance-associated RRs, indicating a conserved similarity.	RESULTS
+59	63	NsrR	protein	Interestingly, two arginine residues (Arg120 and Arg121 in NsrR; Fig 3, shown in purple) at the end of the RDs seem to be strictly conserved throughout the family of response regulators in both the OmpR/PhoB and lantibiotic resistance-associated RRs, indicating a conserved similarity.	RESULTS
+107	110	RDs	structure_element	Interestingly, two arginine residues (Arg120 and Arg121 in NsrR; Fig 3, shown in purple) at the end of the RDs seem to be strictly conserved throughout the family of response regulators in both the OmpR/PhoB and lantibiotic resistance-associated RRs, indicating a conserved similarity.	RESULTS
+122	140	strictly conserved	protein_state	Interestingly, two arginine residues (Arg120 and Arg121 in NsrR; Fig 3, shown in purple) at the end of the RDs seem to be strictly conserved throughout the family of response regulators in both the OmpR/PhoB and lantibiotic resistance-associated RRs, indicating a conserved similarity.	RESULTS
+166	185	response regulators	protein_type	Interestingly, two arginine residues (Arg120 and Arg121 in NsrR; Fig 3, shown in purple) at the end of the RDs seem to be strictly conserved throughout the family of response regulators in both the OmpR/PhoB and lantibiotic resistance-associated RRs, indicating a conserved similarity.	RESULTS
+198	249	OmpR/PhoB and lantibiotic resistance-associated RRs	protein_type	Interestingly, two arginine residues (Arg120 and Arg121 in NsrR; Fig 3, shown in purple) at the end of the RDs seem to be strictly conserved throughout the family of response regulators in both the OmpR/PhoB and lantibiotic resistance-associated RRs, indicating a conserved similarity.	RESULTS
+264	273	conserved	protein_state	Interestingly, two arginine residues (Arg120 and Arg121 in NsrR; Fig 3, shown in purple) at the end of the RDs seem to be strictly conserved throughout the family of response regulators in both the OmpR/PhoB and lantibiotic resistance-associated RRs, indicating a conserved similarity.	RESULTS
+15	25	structures	evidence	As seen in the structures of MtrA and KdpE, this arginine residue residing at the end of α5 participates in the active state dimer interface of the RD through a salt bridge interaction with an aspartate residue.	RESULTS
+29	33	MtrA	protein	As seen in the structures of MtrA and KdpE, this arginine residue residing at the end of α5 participates in the active state dimer interface of the RD through a salt bridge interaction with an aspartate residue.	RESULTS
+38	42	KdpE	protein	As seen in the structures of MtrA and KdpE, this arginine residue residing at the end of α5 participates in the active state dimer interface of the RD through a salt bridge interaction with an aspartate residue.	RESULTS
+49	57	arginine	residue_name	As seen in the structures of MtrA and KdpE, this arginine residue residing at the end of α5 participates in the active state dimer interface of the RD through a salt bridge interaction with an aspartate residue.	RESULTS
+89	91	α5	structure_element	As seen in the structures of MtrA and KdpE, this arginine residue residing at the end of α5 participates in the active state dimer interface of the RD through a salt bridge interaction with an aspartate residue.	RESULTS
+112	118	active	protein_state	As seen in the structures of MtrA and KdpE, this arginine residue residing at the end of α5 participates in the active state dimer interface of the RD through a salt bridge interaction with an aspartate residue.	RESULTS
+125	140	dimer interface	site	As seen in the structures of MtrA and KdpE, this arginine residue residing at the end of α5 participates in the active state dimer interface of the RD through a salt bridge interaction with an aspartate residue.	RESULTS
+148	150	RD	structure_element	As seen in the structures of MtrA and KdpE, this arginine residue residing at the end of α5 participates in the active state dimer interface of the RD through a salt bridge interaction with an aspartate residue.	RESULTS
+161	172	salt bridge	bond_interaction	As seen in the structures of MtrA and KdpE, this arginine residue residing at the end of α5 participates in the active state dimer interface of the RD through a salt bridge interaction with an aspartate residue.	RESULTS
+193	202	aspartate	residue_name	As seen in the structures of MtrA and KdpE, this arginine residue residing at the end of α5 participates in the active state dimer interface of the RD through a salt bridge interaction with an aspartate residue.	RESULTS
+5	14	aspartate	residue_name	This aspartate residue is identified in NsrR as Asp99 (see above).	RESULTS
+40	44	NsrR	protein	This aspartate residue is identified in NsrR as Asp99 (see above).	RESULTS
+48	53	Asp99	residue_name_number	This aspartate residue is identified in NsrR as Asp99 (see above).	RESULTS
+0	12	Arginine 121	residue_name_number	Arginine 121 of NsrR points towards this Asp99 residue however, the distance for a salt bridge interaction is too large.	RESULTS
+16	20	NsrR	protein	Arginine 121 of NsrR points towards this Asp99 residue however, the distance for a salt bridge interaction is too large.	RESULTS
+41	46	Asp99	residue_name_number	Arginine 121 of NsrR points towards this Asp99 residue however, the distance for a salt bridge interaction is too large.	RESULTS
+83	94	salt bridge	bond_interaction	Arginine 121 of NsrR points towards this Asp99 residue however, the distance for a salt bridge interaction is too large.	RESULTS
+21	34	crystallizing	experimental_method	Although we aimed at crystallizing full-length NsrR, this endeavor failed due to proteolytic cleavage within the linker region during the time period of crystallization.	RESULTS
+35	46	full-length	protein_state	Although we aimed at crystallizing full-length NsrR, this endeavor failed due to proteolytic cleavage within the linker region during the time period of crystallization.	RESULTS
+47	51	NsrR	protein	Although we aimed at crystallizing full-length NsrR, this endeavor failed due to proteolytic cleavage within the linker region during the time period of crystallization.	RESULTS
+113	126	linker region	structure_element	Although we aimed at crystallizing full-length NsrR, this endeavor failed due to proteolytic cleavage within the linker region during the time period of crystallization.	RESULTS
+153	168	crystallization	experimental_method	Although we aimed at crystallizing full-length NsrR, this endeavor failed due to proteolytic cleavage within the linker region during the time period of crystallization.	RESULTS
+17	27	structures	evidence	Nonetheless, the structures of NsrR-RD and NsrR-ED together provide the required structural knowledge to predict the linker region that joins the receiver and effector domains.	RESULTS
+31	35	NsrR	protein	Nonetheless, the structures of NsrR-RD and NsrR-ED together provide the required structural knowledge to predict the linker region that joins the receiver and effector domains.	RESULTS
+36	38	RD	structure_element	Nonetheless, the structures of NsrR-RD and NsrR-ED together provide the required structural knowledge to predict the linker region that joins the receiver and effector domains.	RESULTS
+43	47	NsrR	protein	Nonetheless, the structures of NsrR-RD and NsrR-ED together provide the required structural knowledge to predict the linker region that joins the receiver and effector domains.	RESULTS
+48	50	ED	structure_element	Nonetheless, the structures of NsrR-RD and NsrR-ED together provide the required structural knowledge to predict the linker region that joins the receiver and effector domains.	RESULTS
+117	130	linker region	structure_element	Nonetheless, the structures of NsrR-RD and NsrR-ED together provide the required structural knowledge to predict the linker region that joins the receiver and effector domains.	RESULTS
+146	175	receiver and effector domains	structure_element	Nonetheless, the structures of NsrR-RD and NsrR-ED together provide the required structural knowledge to predict the linker region that joins the receiver and effector domains.	RESULTS
+4	17	linker region	structure_element	The linker region of NsrR consists of approximately nine residues (Fig 3), comprising 120RRSQQFIQQ128 (underlined residues are neither present in the structure of RD nor in ED of NsrR) and contains two positively charged amino acids.	RESULTS
+21	25	NsrR	protein	The linker region of NsrR consists of approximately nine residues (Fig 3), comprising 120RRSQQFIQQ128 (underlined residues are neither present in the structure of RD nor in ED of NsrR) and contains two positively charged amino acids.	RESULTS
+86	101	120RRSQQFIQQ128	structure_element	The linker region of NsrR consists of approximately nine residues (Fig 3), comprising 120RRSQQFIQQ128 (underlined residues are neither present in the structure of RD nor in ED of NsrR) and contains two positively charged amino acids.	RESULTS
+150	159	structure	evidence	The linker region of NsrR consists of approximately nine residues (Fig 3), comprising 120RRSQQFIQQ128 (underlined residues are neither present in the structure of RD nor in ED of NsrR) and contains two positively charged amino acids.	RESULTS
+163	165	RD	structure_element	The linker region of NsrR consists of approximately nine residues (Fig 3), comprising 120RRSQQFIQQ128 (underlined residues are neither present in the structure of RD nor in ED of NsrR) and contains two positively charged amino acids.	RESULTS
+173	175	ED	structure_element	The linker region of NsrR consists of approximately nine residues (Fig 3), comprising 120RRSQQFIQQ128 (underlined residues are neither present in the structure of RD nor in ED of NsrR) and contains two positively charged amino acids.	RESULTS
+179	183	NsrR	protein	The linker region of NsrR consists of approximately nine residues (Fig 3), comprising 120RRSQQFIQQ128 (underlined residues are neither present in the structure of RD nor in ED of NsrR) and contains two positively charged amino acids.	RESULTS
+0	3	DNA	chemical	DNA-binding mode of NsrR using a full-length model	RESULTS
+20	24	NsrR	protein	DNA-binding mode of NsrR using a full-length model	RESULTS
+33	44	full-length	protein_state	DNA-binding mode of NsrR using a full-length model	RESULTS
+10	20	structures	evidence	Since the structures of both domains of NsrR were determined, we used this structural information together with the available crystal structures of related proteins to create a model of the full-length NsrR in its active and inactive state.	RESULTS
+40	44	NsrR	protein	Since the structures of both domains of NsrR were determined, we used this structural information together with the available crystal structures of related proteins to create a model of the full-length NsrR in its active and inactive state.	RESULTS
+75	97	structural information	evidence	Since the structures of both domains of NsrR were determined, we used this structural information together with the available crystal structures of related proteins to create a model of the full-length NsrR in its active and inactive state.	RESULTS
+126	144	crystal structures	evidence	Since the structures of both domains of NsrR were determined, we used this structural information together with the available crystal structures of related proteins to create a model of the full-length NsrR in its active and inactive state.	RESULTS
+190	201	full-length	protein_state	Since the structures of both domains of NsrR were determined, we used this structural information together with the available crystal structures of related proteins to create a model of the full-length NsrR in its active and inactive state.	RESULTS
+202	206	NsrR	protein	Since the structures of both domains of NsrR were determined, we used this structural information together with the available crystal structures of related proteins to create a model of the full-length NsrR in its active and inactive state.	RESULTS
+214	220	active	protein_state	Since the structures of both domains of NsrR were determined, we used this structural information together with the available crystal structures of related proteins to create a model of the full-length NsrR in its active and inactive state.	RESULTS
+225	233	inactive	protein_state	Since the structures of both domains of NsrR were determined, we used this structural information together with the available crystal structures of related proteins to create a model of the full-length NsrR in its active and inactive state.	RESULTS
+64	75	Dali search	experimental_method	To achieve this, we first carefully analyzed the outcome of the Dali search for each domain and identified structurally highly similar proteins (based on Z-scores and rmsd values) and choose the full-length structures previously reported.	RESULTS
+154	162	Z-scores	evidence	To achieve this, we first carefully analyzed the outcome of the Dali search for each domain and identified structurally highly similar proteins (based on Z-scores and rmsd values) and choose the full-length structures previously reported.	RESULTS
+167	171	rmsd	evidence	To achieve this, we first carefully analyzed the outcome of the Dali search for each domain and identified structurally highly similar proteins (based on Z-scores and rmsd values) and choose the full-length structures previously reported.	RESULTS
+195	206	full-length	protein_state	To achieve this, we first carefully analyzed the outcome of the Dali search for each domain and identified structurally highly similar proteins (based on Z-scores and rmsd values) and choose the full-length structures previously reported.	RESULTS
+207	217	structures	evidence	To achieve this, we first carefully analyzed the outcome of the Dali search for each domain and identified structurally highly similar proteins (based on Z-scores and rmsd values) and choose the full-length structures previously reported.	RESULTS
+63	74	full-length	protein_state	This resulted in a list of possible templates for modeling the full-length structure of NsrR (Table 2).	RESULTS
+75	84	structure	evidence	This resulted in a list of possible templates for modeling the full-length structure of NsrR (Table 2).	RESULTS
+88	92	NsrR	protein	This resulted in a list of possible templates for modeling the full-length structure of NsrR (Table 2).	RESULTS
+13	16	RRs	protein_type	In solution, RRs exist in equilibrium between the active and inactive state, which is shifted towards the active state upon phosphorylation of the ED.	RESULTS
+50	56	active	protein_state	In solution, RRs exist in equilibrium between the active and inactive state, which is shifted towards the active state upon phosphorylation of the ED.	RESULTS
+61	69	inactive	protein_state	In solution, RRs exist in equilibrium between the active and inactive state, which is shifted towards the active state upon phosphorylation of the ED.	RESULTS
+106	112	active	protein_state	In solution, RRs exist in equilibrium between the active and inactive state, which is shifted towards the active state upon phosphorylation of the ED.	RESULTS
+124	139	phosphorylation	ptm	In solution, RRs exist in equilibrium between the active and inactive state, which is shifted towards the active state upon phosphorylation of the ED.	RESULTS
+147	149	ED	structure_element	In solution, RRs exist in equilibrium between the active and inactive state, which is shifted towards the active state upon phosphorylation of the ED.	RESULTS
+39	41	RR	protein_type	This results in oligomerization of the RR and a higher affinity towards DNA.	RESULTS
+72	75	DNA	chemical	This results in oligomerization of the RR and a higher affinity towards DNA.	RESULTS
+43	52	structure	evidence	Based on the above-mentioned criteria, the structure of MtrA from M. tuberculosis, crystallized in an inactive and non-phosphorylated state, seemed best suited for modeling purposes.	RESULTS
+56	60	MtrA	protein	Based on the above-mentioned criteria, the structure of MtrA from M. tuberculosis, crystallized in an inactive and non-phosphorylated state, seemed best suited for modeling purposes.	RESULTS
+66	81	M. tuberculosis	species	Based on the above-mentioned criteria, the structure of MtrA from M. tuberculosis, crystallized in an inactive and non-phosphorylated state, seemed best suited for modeling purposes.	RESULTS
+83	95	crystallized	experimental_method	Based on the above-mentioned criteria, the structure of MtrA from M. tuberculosis, crystallized in an inactive and non-phosphorylated state, seemed best suited for modeling purposes.	RESULTS
+102	110	inactive	protein_state	Based on the above-mentioned criteria, the structure of MtrA from M. tuberculosis, crystallized in an inactive and non-phosphorylated state, seemed best suited for modeling purposes.	RESULTS
+115	133	non-phosphorylated	protein_state	Based on the above-mentioned criteria, the structure of MtrA from M. tuberculosis, crystallized in an inactive and non-phosphorylated state, seemed best suited for modeling purposes.	RESULTS
+17	23	linker	structure_element	Furthermore, the linker between the two domains of MtrA contains nine amino acids and is of similar length as the linker of NsrR. We aligned the NsrR-RD and -ED to the corresponding MtrA domains and evaluated the structure.	RESULTS
+51	55	MtrA	protein	Furthermore, the linker between the two domains of MtrA contains nine amino acids and is of similar length as the linker of NsrR. We aligned the NsrR-RD and -ED to the corresponding MtrA domains and evaluated the structure.	RESULTS
+114	120	linker	structure_element	Furthermore, the linker between the two domains of MtrA contains nine amino acids and is of similar length as the linker of NsrR. We aligned the NsrR-RD and -ED to the corresponding MtrA domains and evaluated the structure.	RESULTS
+124	128	NsrR	protein	Furthermore, the linker between the two domains of MtrA contains nine amino acids and is of similar length as the linker of NsrR. We aligned the NsrR-RD and -ED to the corresponding MtrA domains and evaluated the structure.	RESULTS
+133	140	aligned	experimental_method	Furthermore, the linker between the two domains of MtrA contains nine amino acids and is of similar length as the linker of NsrR. We aligned the NsrR-RD and -ED to the corresponding MtrA domains and evaluated the structure.	RESULTS
+145	149	NsrR	protein	Furthermore, the linker between the two domains of MtrA contains nine amino acids and is of similar length as the linker of NsrR. We aligned the NsrR-RD and -ED to the corresponding MtrA domains and evaluated the structure.	RESULTS
+150	152	RD	structure_element	Furthermore, the linker between the two domains of MtrA contains nine amino acids and is of similar length as the linker of NsrR. We aligned the NsrR-RD and -ED to the corresponding MtrA domains and evaluated the structure.	RESULTS
+158	160	ED	structure_element	Furthermore, the linker between the two domains of MtrA contains nine amino acids and is of similar length as the linker of NsrR. We aligned the NsrR-RD and -ED to the corresponding MtrA domains and evaluated the structure.	RESULTS
+182	186	MtrA	protein	Furthermore, the linker between the two domains of MtrA contains nine amino acids and is of similar length as the linker of NsrR. We aligned the NsrR-RD and -ED to the corresponding MtrA domains and evaluated the structure.	RESULTS
+213	222	structure	evidence	Furthermore, the linker between the two domains of MtrA contains nine amino acids and is of similar length as the linker of NsrR. We aligned the NsrR-RD and -ED to the corresponding MtrA domains and evaluated the structure.	RESULTS
+16	22	closed	protein_state	This mimics the closed inactive conformation of NsrR (Fig 7A; the missing linker is represented as dotted line).	RESULTS
+23	31	inactive	protein_state	This mimics the closed inactive conformation of NsrR (Fig 7A; the missing linker is represented as dotted line).	RESULTS
+48	52	NsrR	protein	This mimics the closed inactive conformation of NsrR (Fig 7A; the missing linker is represented as dotted line).	RESULTS
+66	73	missing	protein_state	This mimics the closed inactive conformation of NsrR (Fig 7A; the missing linker is represented as dotted line).	RESULTS
+74	80	linker	structure_element	This mimics the closed inactive conformation of NsrR (Fig 7A; the missing linker is represented as dotted line).	RESULTS
+9	20	full-length	protein_state	Model of full-length NsrR in its inactive state and active state.	FIG
+21	25	NsrR	protein	Model of full-length NsrR in its inactive state and active state.	FIG
+33	41	inactive	protein_state	Model of full-length NsrR in its inactive state and active state.	FIG
+52	58	active	protein_state	Model of full-length NsrR in its inactive state and active state.	FIG
+4	6	RD	structure_element	The RD domain of NsrR is highlighted in yellow and the ED domain in green with the “recognition helix” colored in cyan. (a) Inactive state conformation: Both domains of NsrR were aligned to the structure of MtrA (not shown), which adopts a closed inactive conformation, to obtain a model of full-length NsrR. Phe101 and Asp187 stabilize this closed conformation.	FIG
+17	21	NsrR	protein	The RD domain of NsrR is highlighted in yellow and the ED domain in green with the “recognition helix” colored in cyan. (a) Inactive state conformation: Both domains of NsrR were aligned to the structure of MtrA (not shown), which adopts a closed inactive conformation, to obtain a model of full-length NsrR. Phe101 and Asp187 stabilize this closed conformation.	FIG
+55	57	ED	structure_element	The RD domain of NsrR is highlighted in yellow and the ED domain in green with the “recognition helix” colored in cyan. (a) Inactive state conformation: Both domains of NsrR were aligned to the structure of MtrA (not shown), which adopts a closed inactive conformation, to obtain a model of full-length NsrR. Phe101 and Asp187 stabilize this closed conformation.	FIG
+84	101	recognition helix	structure_element	The RD domain of NsrR is highlighted in yellow and the ED domain in green with the “recognition helix” colored in cyan. (a) Inactive state conformation: Both domains of NsrR were aligned to the structure of MtrA (not shown), which adopts a closed inactive conformation, to obtain a model of full-length NsrR. Phe101 and Asp187 stabilize this closed conformation.	FIG
+124	132	Inactive	protein_state	The RD domain of NsrR is highlighted in yellow and the ED domain in green with the “recognition helix” colored in cyan. (a) Inactive state conformation: Both domains of NsrR were aligned to the structure of MtrA (not shown), which adopts a closed inactive conformation, to obtain a model of full-length NsrR. Phe101 and Asp187 stabilize this closed conformation.	FIG
+169	173	NsrR	protein	The RD domain of NsrR is highlighted in yellow and the ED domain in green with the “recognition helix” colored in cyan. (a) Inactive state conformation: Both domains of NsrR were aligned to the structure of MtrA (not shown), which adopts a closed inactive conformation, to obtain a model of full-length NsrR. Phe101 and Asp187 stabilize this closed conformation.	FIG
+179	186	aligned	experimental_method	The RD domain of NsrR is highlighted in yellow and the ED domain in green with the “recognition helix” colored in cyan. (a) Inactive state conformation: Both domains of NsrR were aligned to the structure of MtrA (not shown), which adopts a closed inactive conformation, to obtain a model of full-length NsrR. Phe101 and Asp187 stabilize this closed conformation.	FIG
+194	203	structure	evidence	The RD domain of NsrR is highlighted in yellow and the ED domain in green with the “recognition helix” colored in cyan. (a) Inactive state conformation: Both domains of NsrR were aligned to the structure of MtrA (not shown), which adopts a closed inactive conformation, to obtain a model of full-length NsrR. Phe101 and Asp187 stabilize this closed conformation.	FIG
+207	211	MtrA	protein	The RD domain of NsrR is highlighted in yellow and the ED domain in green with the “recognition helix” colored in cyan. (a) Inactive state conformation: Both domains of NsrR were aligned to the structure of MtrA (not shown), which adopts a closed inactive conformation, to obtain a model of full-length NsrR. Phe101 and Asp187 stabilize this closed conformation.	FIG
+240	246	closed	protein_state	The RD domain of NsrR is highlighted in yellow and the ED domain in green with the “recognition helix” colored in cyan. (a) Inactive state conformation: Both domains of NsrR were aligned to the structure of MtrA (not shown), which adopts a closed inactive conformation, to obtain a model of full-length NsrR. Phe101 and Asp187 stabilize this closed conformation.	FIG
+247	255	inactive	protein_state	The RD domain of NsrR is highlighted in yellow and the ED domain in green with the “recognition helix” colored in cyan. (a) Inactive state conformation: Both domains of NsrR were aligned to the structure of MtrA (not shown), which adopts a closed inactive conformation, to obtain a model of full-length NsrR. Phe101 and Asp187 stabilize this closed conformation.	FIG
+291	302	full-length	protein_state	The RD domain of NsrR is highlighted in yellow and the ED domain in green with the “recognition helix” colored in cyan. (a) Inactive state conformation: Both domains of NsrR were aligned to the structure of MtrA (not shown), which adopts a closed inactive conformation, to obtain a model of full-length NsrR. Phe101 and Asp187 stabilize this closed conformation.	FIG
+303	307	NsrR	protein	The RD domain of NsrR is highlighted in yellow and the ED domain in green with the “recognition helix” colored in cyan. (a) Inactive state conformation: Both domains of NsrR were aligned to the structure of MtrA (not shown), which adopts a closed inactive conformation, to obtain a model of full-length NsrR. Phe101 and Asp187 stabilize this closed conformation.	FIG
+309	315	Phe101	residue_name_number	The RD domain of NsrR is highlighted in yellow and the ED domain in green with the “recognition helix” colored in cyan. (a) Inactive state conformation: Both domains of NsrR were aligned to the structure of MtrA (not shown), which adopts a closed inactive conformation, to obtain a model of full-length NsrR. Phe101 and Asp187 stabilize this closed conformation.	FIG
+320	326	Asp187	residue_name_number	The RD domain of NsrR is highlighted in yellow and the ED domain in green with the “recognition helix” colored in cyan. (a) Inactive state conformation: Both domains of NsrR were aligned to the structure of MtrA (not shown), which adopts a closed inactive conformation, to obtain a model of full-length NsrR. Phe101 and Asp187 stabilize this closed conformation.	FIG
+342	348	closed	protein_state	The RD domain of NsrR is highlighted in yellow and the ED domain in green with the “recognition helix” colored in cyan. (a) Inactive state conformation: Both domains of NsrR were aligned to the structure of MtrA (not shown), which adopts a closed inactive conformation, to obtain a model of full-length NsrR. Phe101 and Asp187 stabilize this closed conformation.	FIG
+4	11	missing	protein_state	The missing linker is represented by a dotted line.	FIG
+12	18	linker	structure_element	The missing linker is represented by a dotted line.	FIG
+4	10	Active	protein_state	(b) Active state conformation: A model of full-length NsrR in active conformation based on the alignment of both the domains of NsrR to the structure of DNA bound structure of KdpE (PDB code: 4KNY), adopting an active open conformation, where the other molecule of NsrR is shown in shades of blue with the recognition helix colored in green.	FIG
+42	53	full-length	protein_state	(b) Active state conformation: A model of full-length NsrR in active conformation based on the alignment of both the domains of NsrR to the structure of DNA bound structure of KdpE (PDB code: 4KNY), adopting an active open conformation, where the other molecule of NsrR is shown in shades of blue with the recognition helix colored in green.	FIG
+54	58	NsrR	protein	(b) Active state conformation: A model of full-length NsrR in active conformation based on the alignment of both the domains of NsrR to the structure of DNA bound structure of KdpE (PDB code: 4KNY), adopting an active open conformation, where the other molecule of NsrR is shown in shades of blue with the recognition helix colored in green.	FIG
+62	68	active	protein_state	(b) Active state conformation: A model of full-length NsrR in active conformation based on the alignment of both the domains of NsrR to the structure of DNA bound structure of KdpE (PDB code: 4KNY), adopting an active open conformation, where the other molecule of NsrR is shown in shades of blue with the recognition helix colored in green.	FIG
+95	104	alignment	experimental_method	(b) Active state conformation: A model of full-length NsrR in active conformation based on the alignment of both the domains of NsrR to the structure of DNA bound structure of KdpE (PDB code: 4KNY), adopting an active open conformation, where the other molecule of NsrR is shown in shades of blue with the recognition helix colored in green.	FIG
+128	132	NsrR	protein	(b) Active state conformation: A model of full-length NsrR in active conformation based on the alignment of both the domains of NsrR to the structure of DNA bound structure of KdpE (PDB code: 4KNY), adopting an active open conformation, where the other molecule of NsrR is shown in shades of blue with the recognition helix colored in green.	FIG
+140	149	structure	evidence	(b) Active state conformation: A model of full-length NsrR in active conformation based on the alignment of both the domains of NsrR to the structure of DNA bound structure of KdpE (PDB code: 4KNY), adopting an active open conformation, where the other molecule of NsrR is shown in shades of blue with the recognition helix colored in green.	FIG
+153	162	DNA bound	protein_state	(b) Active state conformation: A model of full-length NsrR in active conformation based on the alignment of both the domains of NsrR to the structure of DNA bound structure of KdpE (PDB code: 4KNY), adopting an active open conformation, where the other molecule of NsrR is shown in shades of blue with the recognition helix colored in green.	FIG
+163	172	structure	evidence	(b) Active state conformation: A model of full-length NsrR in active conformation based on the alignment of both the domains of NsrR to the structure of DNA bound structure of KdpE (PDB code: 4KNY), adopting an active open conformation, where the other molecule of NsrR is shown in shades of blue with the recognition helix colored in green.	FIG
+176	180	KdpE	protein	(b) Active state conformation: A model of full-length NsrR in active conformation based on the alignment of both the domains of NsrR to the structure of DNA bound structure of KdpE (PDB code: 4KNY), adopting an active open conformation, where the other molecule of NsrR is shown in shades of blue with the recognition helix colored in green.	FIG
+211	217	active	protein_state	(b) Active state conformation: A model of full-length NsrR in active conformation based on the alignment of both the domains of NsrR to the structure of DNA bound structure of KdpE (PDB code: 4KNY), adopting an active open conformation, where the other molecule of NsrR is shown in shades of blue with the recognition helix colored in green.	FIG
+218	222	open	protein_state	(b) Active state conformation: A model of full-length NsrR in active conformation based on the alignment of both the domains of NsrR to the structure of DNA bound structure of KdpE (PDB code: 4KNY), adopting an active open conformation, where the other molecule of NsrR is shown in shades of blue with the recognition helix colored in green.	FIG
+265	269	NsrR	protein	(b) Active state conformation: A model of full-length NsrR in active conformation based on the alignment of both the domains of NsrR to the structure of DNA bound structure of KdpE (PDB code: 4KNY), adopting an active open conformation, where the other molecule of NsrR is shown in shades of blue with the recognition helix colored in green.	FIG
+306	323	recognition helix	structure_element	(b) Active state conformation: A model of full-length NsrR in active conformation based on the alignment of both the domains of NsrR to the structure of DNA bound structure of KdpE (PDB code: 4KNY), adopting an active open conformation, where the other molecule of NsrR is shown in shades of blue with the recognition helix colored in green.	FIG
+3	7	MtrA	protein	In MtrA, the two domains interact via the α4-β5-α5 interface of the receiver domain and the end of α7, α7-α8 loop and α8 of the effector domain.	RESULTS
+42	60	α4-β5-α5 interface	site	In MtrA, the two domains interact via the α4-β5-α5 interface of the receiver domain and the end of α7, α7-α8 loop and α8 of the effector domain.	RESULTS
+68	83	receiver domain	structure_element	In MtrA, the two domains interact via the α4-β5-α5 interface of the receiver domain and the end of α7, α7-α8 loop and α8 of the effector domain.	RESULTS
+99	101	α7	structure_element	In MtrA, the two domains interact via the α4-β5-α5 interface of the receiver domain and the end of ��7, α7-α8 loop and α8 of the effector domain.	RESULTS
+103	113	α7-α8 loop	structure_element	In MtrA, the two domains interact via the α4-β5-α5 interface of the receiver domain and the end of α7, α7-α8 loop and α8 of the effector domain.	RESULTS
+118	120	α8	structure_element	In MtrA, the two domains interact via the α4-β5-α5 interface of the receiver domain and the end of α7, α7-α8 loop and α8 of the effector domain.	RESULTS
+128	143	effector domain	structure_element	In MtrA, the two domains interact via the α4-β5-α5 interface of the receiver domain and the end of α7, α7-α8 loop and α8 of the effector domain.	RESULTS
+5	15	interfaces	site	Both interfaces have been shown to form functionally important contact areas in the active state within members of the OmpR/PhoB subfamily.	RESULTS
+84	90	active	protein_state	Both interfaces have been shown to form functionally important contact areas in the active state within members of the OmpR/PhoB subfamily.	RESULTS
+119	138	OmpR/PhoB subfamily	protein_type	Both interfaces have been shown to form functionally important contact areas in the active state within members of the OmpR/PhoB subfamily.	RESULTS
+16	27	full-length	protein_state	In our model of full-length NsrR, a similar orientation between the domains is observed, contributing to the inter-domain interactions.	RESULTS
+28	32	NsrR	protein	In our model of full-length NsrR, a similar orientation between the domains is observed, contributing to the inter-domain interactions.	RESULTS
+4	12	inactive	protein_state	The inactive conformation of MtrA is supported by the orientation of the side chain of Tyr102, which points away from the active Asp56 residue, while the side chain of Tyr102 interacts with Asp190 of the RD of MtrA, thereby stabilizing its closed conformation.	RESULTS
+29	33	MtrA	protein	The inactive conformation of MtrA is supported by the orientation of the side chain of Tyr102, which points away from the active Asp56 residue, while the side chain of Tyr102 interacts with Asp190 of the RD of MtrA, thereby stabilizing its closed conformation.	RESULTS
+87	93	Tyr102	residue_name_number	The inactive conformation of MtrA is supported by the orientation of the side chain of Tyr102, which points away from the active Asp56 residue, while the side chain of Tyr102 interacts with Asp190 of the RD of MtrA, thereby stabilizing its closed conformation.	RESULTS
+122	128	active	protein_state	The inactive conformation of MtrA is supported by the orientation of the side chain of Tyr102, which points away from the active Asp56 residue, while the side chain of Tyr102 interacts with Asp190 of the RD of MtrA, thereby stabilizing its closed conformation.	RESULTS
+129	134	Asp56	residue_name_number	The inactive conformation of MtrA is supported by the orientation of the side chain of Tyr102, which points away from the active Asp56 residue, while the side chain of Tyr102 interacts with Asp190 of the RD of MtrA, thereby stabilizing its closed conformation.	RESULTS
+168	174	Tyr102	residue_name_number	The inactive conformation of MtrA is supported by the orientation of the side chain of Tyr102, which points away from the active Asp56 residue, while the side chain of Tyr102 interacts with Asp190 of the RD of MtrA, thereby stabilizing its closed conformation.	RESULTS
+190	196	Asp190	residue_name_number	The inactive conformation of MtrA is supported by the orientation of the side chain of Tyr102, which points away from the active Asp56 residue, while the side chain of Tyr102 interacts with Asp190 of the RD of MtrA, thereby stabilizing its closed conformation.	RESULTS
+204	206	RD	structure_element	The inactive conformation of MtrA is supported by the orientation of the side chain of Tyr102, which points away from the active Asp56 residue, while the side chain of Tyr102 interacts with Asp190 of the RD of MtrA, thereby stabilizing its closed conformation.	RESULTS
+210	214	MtrA	protein	The inactive conformation of MtrA is supported by the orientation of the side chain of Tyr102, which points away from the active Asp56 residue, while the side chain of Tyr102 interacts with Asp190 of the RD of MtrA, thereby stabilizing its closed conformation.	RESULTS
+240	246	closed	protein_state	The inactive conformation of MtrA is supported by the orientation of the side chain of Tyr102, which points away from the active Asp56 residue, while the side chain of Tyr102 interacts with Asp190 of the RD of MtrA, thereby stabilizing its closed conformation.	RESULTS
+16	20	NsrR	protein	In the model of NsrR, similar amino acids are present, Phe101 (switch residue) and Asp188 (Fig 3, represented by orange boxes) forming a likewise similar network of interaction.	RESULTS
+55	61	Phe101	residue_name_number	In the model of NsrR, similar amino acids are present, Phe101 (switch residue) and Asp188 (Fig 3, represented by orange boxes) forming a likewise similar network of interaction.	RESULTS
+63	77	switch residue	site	In the model of NsrR, similar amino acids are present, Phe101 (switch residue) and Asp188 (Fig 3, represented by orange boxes) forming a likewise similar network of interaction.	RESULTS
+83	89	Asp188	residue_name_number	In the model of NsrR, similar amino acids are present, Phe101 (switch residue) and Asp188 (Fig 3, represented by orange boxes) forming a likewise similar network of interaction.	RESULTS
+32	38	active	protein_state	Next, we were interested in the active conformation of the NsrR protein adopting an active “open” conformation in the dimeric state.	RESULTS
+59	63	NsrR	protein	Next, we were interested in the active conformation of the NsrR protein adopting an active “open” conformation in the dimeric state.	RESULTS
+84	90	active	protein_state	Next, we were interested in the active conformation of the NsrR protein adopting an active “open” conformation in the dimeric state.	RESULTS
+92	96	open	protein_state	Next, we were interested in the active conformation of the NsrR protein adopting an active “open” conformation in the dimeric state.	RESULTS
+118	125	dimeric	oligomeric_state	Next, we were interested in the active conformation of the NsrR protein adopting an active “open” conformation in the dimeric state.	RESULTS
+3	23	compared and aligned	experimental_method	We compared and aligned the NsrR-RD and ED on the dimeric structure of KdpE that was solved in the DNA-bound state (Fig 7B).	RESULTS
+28	32	NsrR	protein	We compared and aligned the NsrR-RD and ED on the dimeric structure of KdpE that was solved in the DNA-bound state (Fig 7B).	RESULTS
+33	35	RD	structure_element	We compared and aligned the NsrR-RD and ED on the dimeric structure of KdpE that was solved in the DNA-bound state (Fig 7B).	RESULTS
+40	42	ED	structure_element	We compared and aligned the NsrR-RD and ED on the dimeric structure of KdpE that was solved in the DNA-bound state (Fig 7B).	RESULTS
+50	57	dimeric	oligomeric_state	We compared and aligned the NsrR-RD and ED on the dimeric structure of KdpE that was solved in the DNA-bound state (Fig 7B).	RESULTS
+58	67	structure	evidence	We compared and aligned the NsrR-RD and ED on the dimeric structure of KdpE that was solved in the DNA-bound state (Fig 7B).	RESULTS
+71	75	KdpE	protein	We compared and aligned the NsrR-RD and ED on the dimeric structure of KdpE that was solved in the DNA-bound state (Fig 7B).	RESULTS
+85	91	solved	experimental_method	We compared and aligned the NsrR-RD and ED on the dimeric structure of KdpE that was solved in the DNA-bound state (Fig 7B).	RESULTS
+99	108	DNA-bound	protein_state	We compared and aligned the NsrR-RD and ED on the dimeric structure of KdpE that was solved in the DNA-bound state (Fig 7B).	RESULTS
+9	22	linker region	structure_element	Also the linker region of KdpE is of similar length as of NsrR, which suggests that the distance in the DNA-bound state between the RD and ED of NsrR will be similar to that in the KdpE active dimer.	RESULTS
+26	30	KdpE	protein	Also the linker region of KdpE is of similar length as of NsrR, which suggests that the distance in the DNA-bound state between the RD and ED of NsrR will be similar to that in the KdpE active dimer.	RESULTS
+58	62	NsrR	protein	Also the linker region of KdpE is of similar length as of NsrR, which suggests that the distance in the DNA-bound state between the RD and ED of NsrR will be similar to that in the KdpE active dimer.	RESULTS
+104	113	DNA-bound	protein_state	Also the linker region of KdpE is of similar length as of NsrR, which suggests that the distance in the DNA-bound state between the RD and ED of NsrR will be similar to that in the KdpE active dimer.	RESULTS
+132	134	RD	structure_element	Also the linker region of KdpE is of similar length as of NsrR, which suggests that the distance in the DNA-bound state between the RD and ED of NsrR will be similar to that in the KdpE active dimer.	RESULTS
+139	141	ED	structure_element	Also the linker region of KdpE is of similar length as of NsrR, which suggests that the distance in the DNA-bound state between the RD and ED of NsrR will be similar to that in the KdpE active dimer.	RESULTS
+145	149	NsrR	protein	Also the linker region of KdpE is of similar length as of NsrR, which suggests that the distance in the DNA-bound state between the RD and ED of NsrR will be similar to that in the KdpE active dimer.	RESULTS
+181	185	KdpE	protein	Also the linker region of KdpE is of similar length as of NsrR, which suggests that the distance in the DNA-bound state between the RD and ED of NsrR will be similar to that in the KdpE active dimer.	RESULTS
+186	192	active	protein_state	Also the linker region of KdpE is of similar length as of NsrR, which suggests that the distance in the DNA-bound state between the RD and ED of NsrR will be similar to that in the KdpE active dimer.	RESULTS
+193	198	dimer	oligomeric_state	Also the linker region of KdpE is of similar length as of NsrR, which suggests that the distance in the DNA-bound state between the RD and ED of NsrR will be similar to that in the KdpE active dimer.	RESULTS
+3	15	superimposed	experimental_method	We superimposed the ED of NsrR with the DNA-binding domain of KdpE resulting in a reasonably well-aligned structure (rmsd of 2.6Å over 86 Cα atoms; Table 2).	RESULTS
+20	22	ED	structure_element	We superimposed the ED of NsrR with the DNA-binding domain of KdpE resulting in a reasonably well-aligned structure (rmsd of 2.6Å over 86 Cα atoms; Table 2).	RESULTS
+26	30	NsrR	protein	We superimposed the ED of NsrR with the DNA-binding domain of KdpE resulting in a reasonably well-aligned structure (rmsd of 2.6Å over 86 Cα atoms; Table 2).	RESULTS
+40	58	DNA-binding domain	structure_element	We superimposed the ED of NsrR with the DNA-binding domain of KdpE resulting in a reasonably well-aligned structure (rmsd of 2.6Å over 86 Cα atoms; Table 2).	RESULTS
+62	66	KdpE	protein	We superimposed the ED of NsrR with the DNA-binding domain of KdpE resulting in a reasonably well-aligned structure (rmsd of 2.6Å over 86 Cα atoms; Table 2).	RESULTS
+106	115	structure	evidence	We superimposed the ED of NsrR with the DNA-binding domain of KdpE resulting in a reasonably well-aligned structure (rmsd of 2.6Å over 86 Cα atoms; Table 2).	RESULTS
+117	121	rmsd	evidence	We superimposed the ED of NsrR with the DNA-binding domain of KdpE resulting in a reasonably well-aligned structure (rmsd of 2.6Å over 86 Cα atoms; Table 2).	RESULTS
+15	37	highly positive groove	site	As a result, a highly positive groove is created by the two ED domains of NsrR which likely represents the DNA binding site as observed in KdpE. A prediction of the putative promoter sequence that NsrR binds via the BPROM online server was performed (S3 Fig).	RESULTS
+60	62	ED	structure_element	As a result, a highly positive groove is created by the two ED domains of NsrR which likely represents the DNA binding site as observed in KdpE. A prediction of the putative promoter sequence that NsrR binds via the BPROM online server was performed (S3 Fig).	RESULTS
+74	78	NsrR	protein	As a result, a highly positive groove is created by the two ED domains of NsrR which likely represents the DNA binding site as observed in KdpE. A prediction of the putative promoter sequence that NsrR binds via the BPROM online server was performed (S3 Fig).	RESULTS
+107	123	DNA binding site	site	As a result, a highly positive groove is created by the two ED domains of NsrR which likely represents the DNA binding site as observed in KdpE. A prediction of the putative promoter sequence that NsrR binds via the BPROM online server was performed (S3 Fig).	RESULTS
+139	143	KdpE	protein	As a result, a highly positive groove is created by the two ED domains of NsrR which likely represents the DNA binding site as observed in KdpE. A prediction of the putative promoter sequence that NsrR binds via the BPROM online server was performed (S3 Fig).	RESULTS
+197	201	NsrR	protein	As a result, a highly positive groove is created by the two ED domains of NsrR which likely represents the DNA binding site as observed in KdpE. A prediction of the putative promoter sequence that NsrR binds via the BPROM online server was performed (S3 Fig).	RESULTS
+49	52	nsr	gene	A promoter region was identified upstream of the nsr operon.	RESULTS
+58	61	DNA	chemical	However, the regulation of the predicted promoter and the DNA binding by NsrR has to be confirmed.	RESULTS
+73	77	NsrR	protein	However, the regulation of the predicted promoter and the DNA binding by NsrR has to be confirmed.	RESULTS
+23	31	bacteria	taxonomy_domain	In numerous pathogenic bacteria such as S. agalactiae, S. aureus, and C. difficile that apparently do not produce a lantibiotic, a gene cluster is present to provide resistance against lantibiotics such as nisin, nukacin ISK-1, lacticin 481 gallidermin, actagardine, or mersacidin.	RESULTS
+40	53	S. agalactiae	species	In numerous pathogenic bacteria such as S. agalactiae, S. aureus, and C. difficile that apparently do not produce a lantibiotic, a gene cluster is present to provide resistance against lantibiotics such as nisin, nukacin ISK-1, lacticin 481 gallidermin, actagardine, or mersacidin.	RESULTS
+55	64	S. aureus	species	In numerous pathogenic bacteria such as S. agalactiae, S. aureus, and C. difficile that apparently do not produce a lantibiotic, a gene cluster is present to provide resistance against lantibiotics such as nisin, nukacin ISK-1, lacticin 481 gallidermin, actagardine, or mersacidin.	RESULTS
+70	82	C. difficile	species	In numerous pathogenic bacteria such as S. agalactiae, S. aureus, and C. difficile that apparently do not produce a lantibiotic, a gene cluster is present to provide resistance against lantibiotics such as nisin, nukacin ISK-1, lacticin 481 gallidermin, actagardine, or mersacidin.	RESULTS
+116	127	lantibiotic	chemical	In numerous pathogenic bacteria such as S. agalactiae, S. aureus, and C. difficile that apparently do not produce a lantibiotic, a gene cluster is present to provide resistance against lantibiotics such as nisin, nukacin ISK-1, lacticin 481 gallidermin, actagardine, or mersacidin.	RESULTS
+185	197	lantibiotics	chemical	In numerous pathogenic bacteria such as S. agalactiae, S. aureus, and C. difficile that apparently do not produce a lantibiotic, a gene cluster is present to provide resistance against lantibiotics such as nisin, nukacin ISK-1, lacticin 481 gallidermin, actagardine, or mersacidin.	RESULTS
+206	211	nisin	chemical	In numerous pathogenic bacteria such as S. agalactiae, S. aureus, and C. difficile that apparently do not produce a lantibiotic, a gene cluster is present to provide resistance against lantibiotics such as nisin, nukacin ISK-1, lacticin 481 gallidermin, actagardine, or mersacidin.	RESULTS
+213	226	nukacin ISK-1	chemical	In numerous pathogenic bacteria such as S. agalactiae, S. aureus, and C. difficile that apparently do not produce a lantibiotic, a gene cluster is present to provide resistance against lantibiotics such as nisin, nukacin ISK-1, lacticin 481 gallidermin, actagardine, or mersacidin.	RESULTS
+228	240	lacticin 481	chemical	In numerous pathogenic bacteria such as S. agalactiae, S. aureus, and C. difficile that apparently do not produce a lantibiotic, a gene cluster is present to provide resistance against lantibiotics such as nisin, nukacin ISK-1, lacticin 481 gallidermin, actagardine, or mersacidin.	RESULTS
+241	252	gallidermin	chemical	In numerous pathogenic bacteria such as S. agalactiae, S. aureus, and C. difficile that apparently do not produce a lantibiotic, a gene cluster is present to provide resistance against lantibiotics such as nisin, nukacin ISK-1, lacticin 481 gallidermin, actagardine, or mersacidin.	RESULTS
+254	265	actagardine	chemical	In numerous pathogenic bacteria such as S. agalactiae, S. aureus, and C. difficile that apparently do not produce a lantibiotic, a gene cluster is present to provide resistance against lantibiotics such as nisin, nukacin ISK-1, lacticin 481 gallidermin, actagardine, or mersacidin.	RESULTS
+270	280	mersacidin	chemical	In numerous pathogenic bacteria such as S. agalactiae, S. aureus, and C. difficile that apparently do not produce a lantibiotic, a gene cluster is present to provide resistance against lantibiotics such as nisin, nukacin ISK-1, lacticin 481 gallidermin, actagardine, or mersacidin.	RESULTS
+4	13	structure	evidence	The structure of the response regulator NsrR from S. agalactiae presented in this study is the first structural information available for the subgroup of lantibiotic resistance-associated RRs.	RESULTS
+21	39	response regulator	protein_type	The structure of the response regulator NsrR from S. agalactiae presented in this study is the first structural information available for the subgroup of lantibiotic resistance-associated RRs.	RESULTS
+40	44	NsrR	protein	The structure of the response regulator NsrR from S. agalactiae presented in this study is the first structural information available for the subgroup of lantibiotic resistance-associated RRs.	RESULTS
+50	63	S. agalactiae	species	The structure of the response regulator NsrR from S. agalactiae presented in this study is the first structural information available for the subgroup of lantibiotic resistance-associated RRs.	RESULTS
+154	191	lantibiotic resistance-associated RRs	protein_type	The structure of the response regulator NsrR from S. agalactiae presented in this study is the first structural information available for the subgroup of lantibiotic resistance-associated RRs.	RESULTS