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 α7, 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