diff --git "a/annotation_CSV/PMC4817029.csv" "b/annotation_CSV/PMC4817029.csv"
new file mode 100644--- /dev/null
+++ "b/annotation_CSV/PMC4817029.csv"
@@ -0,0 +1,898 @@
+anno_start	anno_end	anno_text	entity_type	sentence	section
+32	60	family 5 glycoside hydrolase	protein_type	Molecular characterization of a family 5 glycoside hydrolase suggests an induced-fit enzymatic mechanism	TITLE
+0	20	Glycoside hydrolases	protein_type	Glycoside hydrolases (GHs) play fundamental roles in the decomposition of lignocellulosic biomaterials.	ABSTRACT
+22	25	GHs	protein_type	Glycoside hydrolases (GHs) play fundamental roles in the decomposition of lignocellulosic biomaterials.	ABSTRACT
+20	31	full-length	protein_state	Here, we report the full-length structure of a cellulase from Bacillus licheniformis (BlCel5B), a member of the GH5 subfamily 4 that is entirely dependent on its two ancillary modules (Ig-like module and CBM46) for catalytic activity.	ABSTRACT
+32	41	structure	evidence	Here, we report the full-length structure of a cellulase from Bacillus licheniformis (BlCel5B), a member of the GH5 subfamily 4 that is entirely dependent on its two ancillary modules (Ig-like module and CBM46) for catalytic activity.	ABSTRACT
+47	56	cellulase	protein_type	Here, we report the full-length structure of a cellulase from Bacillus licheniformis (BlCel5B), a member of the GH5 subfamily 4 that is entirely dependent on its two ancillary modules (Ig-like module and CBM46) for catalytic activity.	ABSTRACT
+62	84	Bacillus licheniformis	species	Here, we report the full-length structure of a cellulase from Bacillus licheniformis (BlCel5B), a member of the GH5 subfamily 4 that is entirely dependent on its two ancillary modules (Ig-like module and CBM46) for catalytic activity.	ABSTRACT
+86	93	BlCel5B	protein	Here, we report the full-length structure of a cellulase from Bacillus licheniformis (BlCel5B), a member of the GH5 subfamily 4 that is entirely dependent on its two ancillary modules (Ig-like module and CBM46) for catalytic activity.	ABSTRACT
+112	127	GH5 subfamily 4	protein_type	Here, we report the full-length structure of a cellulase from Bacillus licheniformis (BlCel5B), a member of the GH5 subfamily 4 that is entirely dependent on its two ancillary modules (Ig-like module and CBM46) for catalytic activity.	ABSTRACT
+166	183	ancillary modules	structure_element	Here, we report the full-length structure of a cellulase from Bacillus licheniformis (BlCel5B), a member of the GH5 subfamily 4 that is entirely dependent on its two ancillary modules (Ig-like module and CBM46) for catalytic activity.	ABSTRACT
+185	199	Ig-like module	structure_element	Here, we report the full-length structure of a cellulase from Bacillus licheniformis (BlCel5B), a member of the GH5 subfamily 4 that is entirely dependent on its two ancillary modules (Ig-like module and CBM46) for catalytic activity.	ABSTRACT
+204	209	CBM46	structure_element	Here, we report the full-length structure of a cellulase from Bacillus licheniformis (BlCel5B), a member of the GH5 subfamily 4 that is entirely dependent on its two ancillary modules (Ig-like module and CBM46) for catalytic activity.	ABSTRACT
+6	27	X-ray crystallography	experimental_method	Using X-ray crystallography, small-angle X-ray scattering and molecular dynamics simulations, we propose that the C-terminal CBM46 caps the distal N-terminal catalytic domain (CD) to establish a fully functional active site via a combination of large-scale multidomain conformational selection and induced-fit mechanisms.	ABSTRACT
+29	57	small-angle X-ray scattering	experimental_method	Using X-ray crystallography, small-angle X-ray scattering and molecular dynamics simulations, we propose that the C-terminal CBM46 caps the distal N-terminal catalytic domain (CD) to establish a fully functional active site via a combination of large-scale multidomain conformational selection and induced-fit mechanisms.	ABSTRACT
+62	92	molecular dynamics simulations	experimental_method	Using X-ray crystallography, small-angle X-ray scattering and molecular dynamics simulations, we propose that the C-terminal CBM46 caps the distal N-terminal catalytic domain (CD) to establish a fully functional active site via a combination of large-scale multidomain conformational selection and induced-fit mechanisms.	ABSTRACT
+125	130	CBM46	structure_element	Using X-ray crystallography, small-angle X-ray scattering and molecular dynamics simulations, we propose that the C-terminal CBM46 caps the distal N-terminal catalytic domain (CD) to establish a fully functional active site via a combination of large-scale multidomain conformational selection and induced-fit mechanisms.	ABSTRACT
+158	174	catalytic domain	structure_element	Using X-ray crystallography, small-angle X-ray scattering and molecular dynamics simulations, we propose that the C-terminal CBM46 caps the distal N-terminal catalytic domain (CD) to establish a fully functional active site via a combination of large-scale multidomain conformational selection and induced-fit mechanisms.	ABSTRACT
+176	178	CD	structure_element	Using X-ray crystallography, small-angle X-ray scattering and molecular dynamics simulations, we propose that the C-terminal CBM46 caps the distal N-terminal catalytic domain (CD) to establish a fully functional active site via a combination of large-scale multidomain conformational selection and induced-fit mechanisms.	ABSTRACT
+195	211	fully functional	protein_state	Using X-ray crystallography, small-angle X-ray scattering and molecular dynamics simulations, we propose that the C-terminal CBM46 caps the distal N-terminal catalytic domain (CD) to establish a fully functional active site via a combination of large-scale multidomain conformational selection and induced-fit mechanisms.	ABSTRACT
+212	223	active site	site	Using X-ray crystallography, small-angle X-ray scattering and molecular dynamics simulations, we propose that the C-terminal CBM46 caps the distal N-terminal catalytic domain (CD) to establish a fully functional active site via a combination of large-scale multidomain conformational selection and induced-fit mechanisms.	ABSTRACT
+4	18	Ig-like module	structure_element	The Ig-like module is pivoting the packing and unpacking motions of CBM46 relative to CD in the assembly of the binding subsite.	ABSTRACT
+68	73	CBM46	structure_element	The Ig-like module is pivoting the packing and unpacking motions of CBM46 relative to CD in the assembly of the binding subsite.	ABSTRACT
+86	88	CD	structure_element	The Ig-like module is pivoting the packing and unpacking motions of CBM46 relative to CD in the assembly of the binding subsite.	ABSTRACT
+112	127	binding subsite	site	The Ig-like module is pivoting the packing and unpacking motions of CBM46 relative to CD in the assembly of the binding subsite.	ABSTRACT
+43	45	GH	protein_type	This is the first example of a multidomain GH relying on large amplitude motions of the CBM46 for assembly of the catalytically competent form of the enzyme.	ABSTRACT
+88	93	CBM46	structure_element	This is the first example of a multidomain GH relying on large amplitude motions of the CBM46 for assembly of the catalytically competent form of the enzyme.	ABSTRACT
+114	137	catalytically competent	protein_state	This is the first example of a multidomain GH relying on large amplitude motions of the CBM46 for assembly of the catalytically competent form of the enzyme.	ABSTRACT
+0	5	Plant	taxonomy_domain	Plant biomass-the most abundant source of carbohydrates on Earth-is primarily composed of cellulose microfibrils surrounded by a hydrated heteropolymeric matrix of hemicellulose and lignin.	INTRO
+42	55	carbohydrates	chemical	Plant biomass-the most abundant source of carbohydrates on Earth-is primarily composed of cellulose microfibrils surrounded by a hydrated heteropolymeric matrix of hemicellulose and lignin.	INTRO
+90	99	cellulose	chemical	Plant biomass-the most abundant source of carbohydrates on Earth-is primarily composed of cellulose microfibrils surrounded by a hydrated heteropolymeric matrix of hemicellulose and lignin.	INTRO
+164	177	hemicellulose	chemical	Plant biomass-the most abundant source of carbohydrates on Earth-is primarily composed of cellulose microfibrils surrounded by a hydrated heteropolymeric matrix of hemicellulose and lignin.	INTRO
+182	188	lignin	chemical	Plant biomass-the most abundant source of carbohydrates on Earth-is primarily composed of cellulose microfibrils surrounded by a hydrated heteropolymeric matrix of hemicellulose and lignin.	INTRO
+0	5	Plant	taxonomy_domain	Plant biomass may be subjected to thermo-chemical pretreatments and enzymatic reactions to produce soluble fermentable sugars.	INTRO
+119	125	sugars	chemical	Plant biomass may be subjected to thermo-chemical pretreatments and enzymatic reactions to produce soluble fermentable sugars.	INTRO
+49	58	cellulose	chemical	The canonical model of hydrolytic degradation of cellulose requires at least three classes of enzymes.	INTRO
+0	18	Cellobiohydrolases	protein_type	Cellobiohydrolases (CBHs) processively cleave the glycosidic bonds at the reducing and non-reducing ends of cellulose chains in crystalline regions to produce cellobiose.	INTRO
+20	24	CBHs	protein_type	Cellobiohydrolases (CBHs) processively cleave the glycosidic bonds at the reducing and non-reducing ends of cellulose chains in crystalline regions to produce cellobiose.	INTRO
+108	117	cellulose	chemical	Cellobiohydrolases (CBHs) processively cleave the glycosidic bonds at the reducing and non-reducing ends of cellulose chains in crystalline regions to produce cellobiose.	INTRO
+159	169	cellobiose	chemical	Cellobiohydrolases (CBHs) processively cleave the glycosidic bonds at the reducing and non-reducing ends of cellulose chains in crystalline regions to produce cellobiose.	INTRO
+0	14	Endoglucanases	protein_type	Endoglucanases (EGs) introduce random cuts in the amorphous regions of cellulose and create new chain extremities for CBH attack; thus, these enzymes act synergistically.	INTRO
+16	19	EGs	protein_type	Endoglucanases (EGs) introduce random cuts in the amorphous regions of cellulose and create new chain extremities for CBH attack; thus, these enzymes act synergistically.	INTRO
+71	80	cellulose	chemical	Endoglucanases (EGs) introduce random cuts in the amorphous regions of cellulose and create new chain extremities for CBH attack; thus, these enzymes act synergistically.	INTRO
+118	121	CBH	protein_type	Endoglucanases (EGs) introduce random cuts in the amorphous regions of cellulose and create new chain extremities for CBH attack; thus, these enzymes act synergistically.	INTRO
+13	23	cellobiose	chemical	The released cellobiose molecules are then enzymatically converted into glucose by β-glucosidases.	INTRO
+72	79	glucose	chemical	The released cellobiose molecules are then enzymatically converted into glucose by β-glucosidases.	INTRO
+83	97	β-glucosidases	protein_type	The released cellobiose molecules are then enzymatically converted into glucose by β-glucosidases.	INTRO
+30	50	glycoside hydrolases	protein_type	The molecular architecture of glycoside hydrolases (GHs) frequently consists of a catalytic domain (CD), where hydrolysis occurs, and one or more ancillary modules (AMs), which are usually connected by less structured linkers.	INTRO
+52	55	GHs	protein_type	The molecular architecture of glycoside hydrolases (GHs) frequently consists of a catalytic domain (CD), where hydrolysis occurs, and one or more ancillary modules (AMs), which are usually connected by less structured linkers.	INTRO
+82	98	catalytic domain	structure_element	The molecular architecture of glycoside hydrolases (GHs) frequently consists of a catalytic domain (CD), where hydrolysis occurs, and one or more ancillary modules (AMs), which are usually connected by less structured linkers.	INTRO
+100	102	CD	structure_element	The molecular architecture of glycoside hydrolases (GHs) frequently consists of a catalytic domain (CD), where hydrolysis occurs, and one or more ancillary modules (AMs), which are usually connected by less structured linkers.	INTRO
+146	163	ancillary modules	structure_element	The molecular architecture of glycoside hydrolases (GHs) frequently consists of a catalytic domain (CD), where hydrolysis occurs, and one or more ancillary modules (AMs), which are usually connected by less structured linkers.	INTRO
+165	168	AMs	structure_element	The molecular architecture of glycoside hydrolases (GHs) frequently consists of a catalytic domain (CD), where hydrolysis occurs, and one or more ancillary modules (AMs), which are usually connected by less structured linkers.	INTRO
+202	217	less structured	protein_state	The molecular architecture of glycoside hydrolases (GHs) frequently consists of a catalytic domain (CD), where hydrolysis occurs, and one or more ancillary modules (AMs), which are usually connected by less structured linkers.	INTRO
+218	225	linkers	structure_element	The molecular architecture of glycoside hydrolases (GHs) frequently consists of a catalytic domain (CD), where hydrolysis occurs, and one or more ancillary modules (AMs), which are usually connected by less structured linkers.	INTRO
+24	27	AMs	structure_element	The most common type of AMs are carbohydrate-binding modules (CBMs), which are able to recognize and bind specific carbohydrate chains.	INTRO
+32	60	carbohydrate-binding modules	structure_element	The most common type of AMs are carbohydrate-binding modules (CBMs), which are able to recognize and bind specific carbohydrate chains.	INTRO
+62	66	CBMs	structure_element	The most common type of AMs are carbohydrate-binding modules (CBMs), which are able to recognize and bind specific carbohydrate chains.	INTRO
+115	127	carbohydrate	chemical	The most common type of AMs are carbohydrate-binding modules (CBMs), which are able to recognize and bind specific carbohydrate chains.	INTRO
+59	63	CBMs	structure_element	Generally distinct and independent structural domains, the CBMs facilitate carbohydrate hydrolysis by increasing the local concentration of enzymes at the surface of insoluble substrates, thereby targeting the CD component to its cognate ligands.	INTRO
+75	87	carbohydrate	chemical	Generally distinct and independent structural domains, the CBMs facilitate carbohydrate hydrolysis by increasing the local concentration of enzymes at the surface of insoluble substrates, thereby targeting the CD component to its cognate ligands.	INTRO
+210	212	CD	structure_element	Generally distinct and independent structural domains, the CBMs facilitate carbohydrate hydrolysis by increasing the local concentration of enzymes at the surface of insoluble substrates, thereby targeting the CD component to its cognate ligands.	INTRO
+0	4	CBMs	structure_element	CBMs might also disrupt the crystalline structure of cellulose microfibrils, although the underlying mechanism remains poorly understood.	INTRO
+53	62	cellulose	chemical	CBMs might also disrupt the crystalline structure of cellulose microfibrils, although the underlying mechanism remains poorly understood.	INTRO
+6	10	CBMs	structure_element	Thus, CBMs enhance the accessibility of CDs to carbohydrate chains to improve enzymatic activity, making them important candidates for the development of effective biomass-degrading enzymes in industrial settings.	INTRO
+40	43	CDs	structure_element	Thus, CBMs enhance the accessibility of CDs to carbohydrate chains to improve enzymatic activity, making them important candidates for the development of effective biomass-degrading enzymes in industrial settings.	INTRO
+47	59	carbohydrate	chemical	Thus, CBMs enhance the accessibility of CDs to carbohydrate chains to improve enzymatic activity, making them important candidates for the development of effective biomass-degrading enzymes in industrial settings.	INTRO
+31	37	active	protein_state	Although there are examples of active GHs that lack AMs, the majority of the enzymes depend on AMs for activity.	INTRO
+38	41	GHs	protein_type	Although there are examples of active GHs that lack AMs, the majority of the enzymes depend on AMs for activity.	INTRO
+47	51	lack	protein_state	Although there are examples of active GHs that lack AMs, the majority of the enzymes depend on AMs for activity.	INTRO
+52	55	AMs	structure_element	Although there are examples of active GHs that lack AMs, the majority of the enzymes depend on AMs for activity.	INTRO
+95	98	AMs	structure_element	Although there are examples of active GHs that lack AMs, the majority of the enzymes depend on AMs for activity.	INTRO
+18	22	CBMs	structure_element	In several cases, CBMs were shown to extend and complement the CD substrate-binding site in multimodular carbohydrate-active enzymes, such as endo/exocellulase E4 from Thermobifida fusca, chitinase B from Serratia marcescens, a starch phosphatase from Arabidopsis thaliana and a GH5 subfamily 4 (GH5_4) endoglucanase from Bacillus halodurans (BhCel5B).	INTRO
+63	65	CD	structure_element	In several cases, CBMs were shown to extend and complement the CD substrate-binding site in multimodular carbohydrate-active enzymes, such as endo/exocellulase E4 from Thermobifida fusca, chitinase B from Serratia marcescens, a starch phosphatase from Arabidopsis thaliana and a GH5 subfamily 4 (GH5_4) endoglucanase from Bacillus halodurans (BhCel5B).	INTRO
+66	88	substrate-binding site	site	In several cases, CBMs were shown to extend and complement the CD substrate-binding site in multimodular carbohydrate-active enzymes, such as endo/exocellulase E4 from Thermobifida fusca, chitinase B from Serratia marcescens, a starch phosphatase from Arabidopsis thaliana and a GH5 subfamily 4 (GH5_4) endoglucanase from Bacillus halodurans (BhCel5B).	INTRO
+105	132	carbohydrate-active enzymes	protein_type	In several cases, CBMs were shown to extend and complement the CD substrate-binding site in multimodular carbohydrate-active enzymes, such as endo/exocellulase E4 from Thermobifida fusca, chitinase B from Serratia marcescens, a starch phosphatase from Arabidopsis thaliana and a GH5 subfamily 4 (GH5_4) endoglucanase from Bacillus halodurans (BhCel5B).	INTRO
+142	159	endo/exocellulase	protein_type	In several cases, CBMs were shown to extend and complement the CD substrate-binding site in multimodular carbohydrate-active enzymes, such as endo/exocellulase E4 from Thermobifida fusca, chitinase B from Serratia marcescens, a starch phosphatase from Arabidopsis thaliana and a GH5 subfamily 4 (GH5_4) endoglucanase from Bacillus halodurans (BhCel5B).	INTRO
+160	162	E4	protein	In several cases, CBMs were shown to extend and complement the CD substrate-binding site in multimodular carbohydrate-active enzymes, such as endo/exocellulase E4 from Thermobifida fusca, chitinase B from Serratia marcescens, a starch phosphatase from Arabidopsis thaliana and a GH5 subfamily 4 (GH5_4) endoglucanase from Bacillus halodurans (BhCel5B).	INTRO
+168	186	Thermobifida fusca	species	In several cases, CBMs were shown to extend and complement the CD substrate-binding site in multimodular carbohydrate-active enzymes, such as endo/exocellulase E4 from Thermobifida fusca, chitinase B from Serratia marcescens, a starch phosphatase from Arabidopsis thaliana and a GH5 subfamily 4 (GH5_4) endoglucanase from Bacillus halodurans (BhCel5B).	INTRO
+188	199	chitinase B	protein	In several cases, CBMs were shown to extend and complement the CD substrate-binding site in multimodular carbohydrate-active enzymes, such as endo/exocellulase E4 from Thermobifida fusca, chitinase B from Serratia marcescens, a starch phosphatase from Arabidopsis thaliana and a GH5 subfamily 4 (GH5_4) endoglucanase from Bacillus halodurans (BhCel5B).	INTRO
+205	224	Serratia marcescens	species	In several cases, CBMs were shown to extend and complement the CD substrate-binding site in multimodular carbohydrate-active enzymes, such as endo/exocellulase E4 from Thermobifida fusca, chitinase B from Serratia marcescens, a starch phosphatase from Arabidopsis thaliana and a GH5 subfamily 4 (GH5_4) endoglucanase from Bacillus halodurans (BhCel5B).	INTRO
+228	246	starch phosphatase	protein_type	In several cases, CBMs were shown to extend and complement the CD substrate-binding site in multimodular carbohydrate-active enzymes, such as endo/exocellulase E4 from Thermobifida fusca, chitinase B from Serratia marcescens, a starch phosphatase from Arabidopsis thaliana and a GH5 subfamily 4 (GH5_4) endoglucanase from Bacillus halodurans (BhCel5B).	INTRO
+252	272	Arabidopsis thaliana	species	In several cases, CBMs were shown to extend and complement the CD substrate-binding site in multimodular carbohydrate-active enzymes, such as endo/exocellulase E4 from Thermobifida fusca, chitinase B from Serratia marcescens, a starch phosphatase from Arabidopsis thaliana and a GH5 subfamily 4 (GH5_4) endoglucanase from Bacillus halodurans (BhCel5B).	INTRO
+279	294	GH5 subfamily 4	protein_type	In several cases, CBMs were shown to extend and complement the CD substrate-binding site in multimodular carbohydrate-active enzymes, such as endo/exocellulase E4 from Thermobifida fusca, chitinase B from Serratia marcescens, a starch phosphatase from Arabidopsis thaliana and a GH5 subfamily 4 (GH5_4) endoglucanase from Bacillus halodurans (BhCel5B).	INTRO
+296	301	GH5_4	protein_type	In several cases, CBMs were shown to extend and complement the CD substrate-binding site in multimodular carbohydrate-active enzymes, such as endo/exocellulase E4 from Thermobifida fusca, chitinase B from Serratia marcescens, a starch phosphatase from Arabidopsis thaliana and a GH5 subfamily 4 (GH5_4) endoglucanase from Bacillus halodurans (BhCel5B).	INTRO
+303	316	endoglucanase	protein_type	In several cases, CBMs were shown to extend and complement the CD substrate-binding site in multimodular carbohydrate-active enzymes, such as endo/exocellulase E4 from Thermobifida fusca, chitinase B from Serratia marcescens, a starch phosphatase from Arabidopsis thaliana and a GH5 subfamily 4 (GH5_4) endoglucanase from Bacillus halodurans (BhCel5B).	INTRO
+322	341	Bacillus halodurans	species	In several cases, CBMs were shown to extend and complement the CD substrate-binding site in multimodular carbohydrate-active enzymes, such as endo/exocellulase E4 from Thermobifida fusca, chitinase B from Serratia marcescens, a starch phosphatase from Arabidopsis thaliana and a GH5 subfamily 4 (GH5_4) endoglucanase from Bacillus halodurans (BhCel5B).	INTRO
+343	350	BhCel5B	protein	In several cases, CBMs were shown to extend and complement the CD substrate-binding site in multimodular carbohydrate-active enzymes, such as endo/exocellulase E4 from Thermobifida fusca, chitinase B from Serratia marcescens, a starch phosphatase from Arabidopsis thaliana and a GH5 subfamily 4 (GH5_4) endoglucanase from Bacillus halodurans (BhCel5B).	INTRO
+79	82	GH9	protein_type	A pioneer work of Sakon et al. revealed that rigid structural extension of the GH9 CD by a type C CBM3 imprints a processive mode of action to this endoglucanase.	INTRO
+83	85	CD	structure_element	A pioneer work of Sakon et al. revealed that rigid structural extension of the GH9 CD by a type C CBM3 imprints a processive mode of action to this endoglucanase.	INTRO
+91	102	type C CBM3	structure_element	A pioneer work of Sakon et al. revealed that rigid structural extension of the GH9 CD by a type C CBM3 imprints a processive mode of action to this endoglucanase.	INTRO
+148	161	endoglucanase	protein_type	A pioneer work of Sakon et al. revealed that rigid structural extension of the GH9 CD by a type C CBM3 imprints a processive mode of action to this endoglucanase.	INTRO
+33	36	CBM	structure_element	Further publications showed that CBM-based structural extensions of the active site are important for substrate engagement and recognition.	INTRO
+72	83	active site	site	Further publications showed that CBM-based structural extensions of the active site are important for substrate engagement and recognition.	INTRO
+39	54	X-ray structure	evidence	Recently, Venditto et al. reported the X-ray structure of the tri-modular GH5_4 endoglucanase from Bacillus halodurans (31% sequence identity to BlCel5B), with the CBM46 extension of the active site appended to the CD via an immunoglobulin (Ig)-like module.	INTRO
+62	73	tri-modular	structure_element	Recently, Venditto et al. reported the X-ray structure of the tri-modular GH5_4 endoglucanase from Bacillus halodurans (31% sequence identity to BlCel5B), with the CBM46 extension of the active site appended to the CD via an immunoglobulin (Ig)-like module.	INTRO
+74	79	GH5_4	protein_type	Recently, Venditto et al. reported the X-ray structure of the tri-modular GH5_4 endoglucanase from Bacillus halodurans (31% sequence identity to BlCel5B), with the CBM46 extension of the active site appended to the CD via an immunoglobulin (Ig)-like module.	INTRO
+80	93	endoglucanase	protein_type	Recently, Venditto et al. reported the X-ray structure of the tri-modular GH5_4 endoglucanase from Bacillus halodurans (31% sequence identity to BlCel5B), with the CBM46 extension of the active site appended to the CD via an immunoglobulin (Ig)-like module.	INTRO
+99	118	Bacillus halodurans	species	Recently, Venditto et al. reported the X-ray structure of the tri-modular GH5_4 endoglucanase from Bacillus halodurans (31% sequence identity to BlCel5B), with the CBM46 extension of the active site appended to the CD via an immunoglobulin (Ig)-like module.	INTRO
+145	152	BlCel5B	protein	Recently, Venditto et al. reported the X-ray structure of the tri-modular GH5_4 endoglucanase from Bacillus halodurans (31% sequence identity to BlCel5B), with the CBM46 extension of the active site appended to the CD via an immunoglobulin (Ig)-like module.	INTRO
+164	169	CBM46	structure_element	Recently, Venditto et al. reported the X-ray structure of the tri-modular GH5_4 endoglucanase from Bacillus halodurans (31% sequence identity to BlCel5B), with the CBM46 extension of the active site appended to the CD via an immunoglobulin (Ig)-like module.	INTRO
+187	198	active site	site	Recently, Venditto et al. reported the X-ray structure of the tri-modular GH5_4 endoglucanase from Bacillus halodurans (31% sequence identity to BlCel5B), with the CBM46 extension of the active site appended to the CD via an immunoglobulin (Ig)-like module.	INTRO
+215	217	CD	structure_element	Recently, Venditto et al. reported the X-ray structure of the tri-modular GH5_4 endoglucanase from Bacillus halodurans (31% sequence identity to BlCel5B), with the CBM46 extension of the active site appended to the CD via an immunoglobulin (Ig)-like module.	INTRO
+225	256	immunoglobulin (Ig)-like module	structure_element	Recently, Venditto et al. reported the X-ray structure of the tri-modular GH5_4 endoglucanase from Bacillus halodurans (31% sequence identity to BlCel5B), with the CBM46 extension of the active site appended to the CD via an immunoglobulin (Ig)-like module.	INTRO
+0	10	Removal of	experimental_method	Removal of the CBM46 caused a ~60-fold reduction of the activity of the enzyme against β-glucans, but showed little or no effect against xyloglucan hydrolysis.	INTRO
+15	20	CBM46	structure_element	Removal of the CBM46 caused a ~60-fold reduction of the activity of the enzyme against β-glucans, but showed little or no effect against xyloglucan hydrolysis.	INTRO
+87	96	β-glucans	chemical	Removal of the CBM46 caused a ~60-fold reduction of the activity of the enzyme against β-glucans, but showed little or no effect against xyloglucan hydrolysis.	INTRO
+137	147	xyloglucan	chemical	Removal of the CBM46 caused a ~60-fold reduction of the activity of the enzyme against β-glucans, but showed little or no effect against xyloglucan hydrolysis.	INTRO
+14	19	CBM46	structure_element	Moreover, the CBM46 mediated a significant increase in the BhCel5B activity in plant cell wall settings.	INTRO
+59	66	BhCel5B	protein	Moreover, the CBM46 mediated a significant increase in the BhCel5B activity in plant cell wall settings.	INTRO
+79	84	plant	taxonomy_domain	Moreover, the CBM46 mediated a significant increase in the BhCel5B activity in plant cell wall settings.	INTRO
+0	8	Modeling	experimental_method	Modeling of cellotriose in the negative subsites of the active site of BhCel5B demonstrated the structural conservation of the -1 position, but provided little information about direct interactions between CBM46 and the substrate.	INTRO
+12	23	cellotriose	chemical	Modeling of cellotriose in the negative subsites of the active site of BhCel5B demonstrated the structural conservation of the -1 position, but provided little information about direct interactions between CBM46 and the substrate.	INTRO
+31	48	negative subsites	site	Modeling of cellotriose in the negative subsites of the active site of BhCel5B demonstrated the structural conservation of the -1 position, but provided little information about direct interactions between CBM46 and the substrate.	INTRO
+56	67	active site	site	Modeling of cellotriose in the negative subsites of the active site of BhCel5B demonstrated the structural conservation of the -1 position, but provided little information about direct interactions between CBM46 and the substrate.	INTRO
+71	78	BhCel5B	protein	Modeling of cellotriose in the negative subsites of the active site of BhCel5B demonstrated the structural conservation of the -1 position, but provided little information about direct interactions between CBM46 and the substrate.	INTRO
+96	119	structural conservation	protein_state	Modeling of cellotriose in the negative subsites of the active site of BhCel5B demonstrated the structural conservation of the -1 position, but provided little information about direct interactions between CBM46 and the substrate.	INTRO
+127	129	-1	residue_number	Modeling of cellotriose in the negative subsites of the active site of BhCel5B demonstrated the structural conservation of the -1 position, but provided little information about direct interactions between CBM46 and the substrate.	INTRO
+206	211	CBM46	structure_element	Modeling of cellotriose in the negative subsites of the active site of BhCel5B demonstrated the structural conservation of the -1 position, but provided little information about direct interactions between CBM46 and the substrate.	INTRO
+41	49	β-glucan	chemical	It was speculated that β-1,3 kink of the β-glucan might allow the ligand to reach for the CBM46, whereas pure β-1,4 linkages in the backbone of xyloglucan chains would restrict binding to the CD, thus explaining the lack of influence of the CBM46 on the enzymatic activity of BhCel5B against xyloglucans in solution.	INTRO
+90	95	CBM46	structure_element	It was speculated that β-1,3 kink of the β-glucan might allow the ligand to reach for the CBM46, whereas pure β-1,4 linkages in the backbone of xyloglucan chains would restrict binding to the CD, thus explaining the lack of influence of the CBM46 on the enzymatic activity of BhCel5B against xyloglucans in solution.	INTRO
+144	154	xyloglucan	chemical	It was speculated that β-1,3 kink of the β-glucan might allow the ligand to reach for the CBM46, whereas pure β-1,4 linkages in the backbone of xyloglucan chains would restrict binding to the CD, thus explaining the lack of influence of the CBM46 on the enzymatic activity of BhCel5B against xyloglucans in solution.	INTRO
+192	194	CD	structure_element	It was speculated that β-1,3 kink of the β-glucan might allow the ligand to reach for the CBM46, whereas pure β-1,4 linkages in the backbone of xyloglucan chains would restrict binding to the CD, thus explaining the lack of influence of the CBM46 on the enzymatic activity of BhCel5B against xyloglucans in solution.	INTRO
+241	246	CBM46	structure_element	It was speculated that β-1,3 kink of the β-glucan might allow the ligand to reach for the CBM46, whereas pure β-1,4 linkages in the backbone of xyloglucan chains would restrict binding to the CD, thus explaining the lack of influence of the CBM46 on the enzymatic activity of BhCel5B against xyloglucans in solution.	INTRO
+276	283	BhCel5B	protein	It was speculated that β-1,3 kink of the β-glucan might allow the ligand to reach for the CBM46, whereas pure β-1,4 linkages in the backbone of xyloglucan chains would restrict binding to the CD, thus explaining the lack of influence of the CBM46 on the enzymatic activity of BhCel5B against xyloglucans in solution.	INTRO
+292	303	xyloglucans	chemical	It was speculated that β-1,3 kink of the β-glucan might allow the ligand to reach for the CBM46, whereas pure β-1,4 linkages in the backbone of xyloglucan chains would restrict binding to the CD, thus explaining the lack of influence of the CBM46 on the enzymatic activity of BhCel5B against xyloglucans in solution.	INTRO
+28	33	CBM46	structure_element	It was also argued that the CBM46 could potentialize the activity by driving BhCel5B towards xyloglucan-rich regions in the context of the plant cell walls, but no large-scale conformational adjustments of the AMs have been shown to occur or suggested to take part in the enzymatic activity.	INTRO
+77	84	BhCel5B	protein	It was also argued that the CBM46 could potentialize the activity by driving BhCel5B towards xyloglucan-rich regions in the context of the plant cell walls, but no large-scale conformational adjustments of the AMs have been shown to occur or suggested to take part in the enzymatic activity.	INTRO
+93	116	xyloglucan-rich regions	structure_element	It was also argued that the CBM46 could potentialize the activity by driving BhCel5B towards xyloglucan-rich regions in the context of the plant cell walls, but no large-scale conformational adjustments of the AMs have been shown to occur or suggested to take part in the enzymatic activity.	INTRO
+139	144	plant	taxonomy_domain	It was also argued that the CBM46 could potentialize the activity by driving BhCel5B towards xyloglucan-rich regions in the context of the plant cell walls, but no large-scale conformational adjustments of the AMs have been shown to occur or suggested to take part in the enzymatic activity.	INTRO
+210	213	AMs	structure_element	It was also argued that the CBM46 could potentialize the activity by driving BhCel5B towards xyloglucan-rich regions in the context of the plant cell walls, but no large-scale conformational adjustments of the AMs have been shown to occur or suggested to take part in the enzymatic activity.	INTRO
+145	153	extended	protein_state	Although initially introduced as contradictory theories, these two limiting cases can be unified considering the flux description concept or the extended conformational selection model.	INTRO
+77	104	carbohydrate-active enzymes	protein_type	While local ligand-induced conformational adjustments have been reported for carbohydrate-active enzymes, cognate ligands recognition and hydrolysis mediated by a large-scale conformational mobility of distinct domains in multidomain settings is uncommon for endoglucanases.	INTRO
+259	273	endoglucanases	protein_type	While local ligand-induced conformational adjustments have been reported for carbohydrate-active enzymes, cognate ligands recognition and hydrolysis mediated by a large-scale conformational mobility of distinct domains in multidomain settings is uncommon for endoglucanases.	INTRO
+20	37	crystal structure	evidence	Here, we report the crystal structure of a full-length GH5_4 enzyme from Bacillus licheniformis (BlCel5B) that exhibits two AMs (Ig-like module and CBM46) appended to the CD.	INTRO
+43	54	full-length	protein_state	Here, we report the crystal structure of a full-length GH5_4 enzyme from Bacillus licheniformis (BlCel5B) that exhibits two AMs (Ig-like module and CBM46) appended to the CD.	INTRO
+55	60	GH5_4	protein_type	Here, we report the crystal structure of a full-length GH5_4 enzyme from Bacillus licheniformis (BlCel5B) that exhibits two AMs (Ig-like module and CBM46) appended to the CD.	INTRO
+73	95	Bacillus licheniformis	species	Here, we report the crystal structure of a full-length GH5_4 enzyme from Bacillus licheniformis (BlCel5B) that exhibits two AMs (Ig-like module and CBM46) appended to the CD.	INTRO
+97	104	BlCel5B	protein	Here, we report the crystal structure of a full-length GH5_4 enzyme from Bacillus licheniformis (BlCel5B) that exhibits two AMs (Ig-like module and CBM46) appended to the CD.	INTRO
+124	127	AMs	structure_element	Here, we report the crystal structure of a full-length GH5_4 enzyme from Bacillus licheniformis (BlCel5B) that exhibits two AMs (Ig-like module and CBM46) appended to the CD.	INTRO
+129	143	Ig-like module	structure_element	Here, we report the crystal structure of a full-length GH5_4 enzyme from Bacillus licheniformis (BlCel5B) that exhibits two AMs (Ig-like module and CBM46) appended to the CD.	INTRO
+148	153	CBM46	structure_element	Here, we report the crystal structure of a full-length GH5_4 enzyme from Bacillus licheniformis (BlCel5B) that exhibits two AMs (Ig-like module and CBM46) appended to the CD.	INTRO
+171	173	CD	structure_element	Here, we report the crystal structure of a full-length GH5_4 enzyme from Bacillus licheniformis (BlCel5B) that exhibits two AMs (Ig-like module and CBM46) appended to the CD.	INTRO
+3	45	structurally and functionally characterize	experimental_method	We structurally and functionally characterize the enzyme using a combination of protein crystallography, small-angle X-ray scattering (SAXS), molecular dynamics computer simulations and site-directed mutagenesis, and show that the AMs and their conformational mobility are essential for the enzymatic activity of BlCel5B.	INTRO
+80	103	protein crystallography	experimental_method	We structurally and functionally characterize the enzyme using a combination of protein crystallography, small-angle X-ray scattering (SAXS), molecular dynamics computer simulations and site-directed mutagenesis, and show that the AMs and their conformational mobility are essential for the enzymatic activity of BlCel5B.	INTRO
+105	133	small-angle X-ray scattering	experimental_method	We structurally and functionally characterize the enzyme using a combination of protein crystallography, small-angle X-ray scattering (SAXS), molecular dynamics computer simulations and site-directed mutagenesis, and show that the AMs and their conformational mobility are essential for the enzymatic activity of BlCel5B.	INTRO
+135	139	SAXS	experimental_method	We structurally and functionally characterize the enzyme using a combination of protein crystallography, small-angle X-ray scattering (SAXS), molecular dynamics computer simulations and site-directed mutagenesis, and show that the AMs and their conformational mobility are essential for the enzymatic activity of BlCel5B.	INTRO
+142	181	molecular dynamics computer simulations	experimental_method	We structurally and functionally characterize the enzyme using a combination of protein crystallography, small-angle X-ray scattering (SAXS), molecular dynamics computer simulations and site-directed mutagenesis, and show that the AMs and their conformational mobility are essential for the enzymatic activity of BlCel5B.	INTRO
+186	211	site-directed mutagenesis	experimental_method	We structurally and functionally characterize the enzyme using a combination of protein crystallography, small-angle X-ray scattering (SAXS), molecular dynamics computer simulations and site-directed mutagenesis, and show that the AMs and their conformational mobility are essential for the enzymatic activity of BlCel5B.	INTRO
+231	234	AMs	structure_element	We structurally and functionally characterize the enzyme using a combination of protein crystallography, small-angle X-ray scattering (SAXS), molecular dynamics computer simulations and site-directed mutagenesis, and show that the AMs and their conformational mobility are essential for the enzymatic activity of BlCel5B.	INTRO
+313	320	BlCel5B	protein	We structurally and functionally characterize the enzyme using a combination of protein crystallography, small-angle X-ray scattering (SAXS), molecular dynamics computer simulations and site-directed mutagenesis, and show that the AMs and their conformational mobility are essential for the enzymatic activity of BlCel5B.	INTRO
+70	75	CBM46	structure_element	We find that the large-scale conformational adjustments of the distal CBM46 mediated by the Ig-like hinge domain are crucial in active-site assembly for optimal substrate binding and hydrolysis.	INTRO
+92	112	Ig-like hinge domain	structure_element	We find that the large-scale conformational adjustments of the distal CBM46 mediated by the Ig-like hinge domain are crucial in active-site assembly for optimal substrate binding and hydrolysis.	INTRO
+128	139	active-site	site	We find that the large-scale conformational adjustments of the distal CBM46 mediated by the Ig-like hinge domain are crucial in active-site assembly for optimal substrate binding and hydrolysis.	INTRO
+20	27	BlCel5B	protein	We propose that the BlCel5B conformational selection/induced-fit mechanism of hydrolysis represents a novel paradigm that applies to several GH5_4 members and, possibly, to a number of other multidomain GHs.	INTRO
+141	146	GH5_4	protein_type	We propose that the BlCel5B conformational selection/induced-fit mechanism of hydrolysis represents a novel paradigm that applies to several GH5_4 members and, possibly, to a number of other multidomain GHs.	INTRO
+203	206	GHs	protein_type	We propose that the BlCel5B conformational selection/induced-fit mechanism of hydrolysis represents a novel paradigm that applies to several GH5_4 members and, possibly, to a number of other multidomain GHs.	INTRO
+0	7	BlCel5B	protein	BlCel5B Crystal Structure	RESULTS
+8	25	Crystal Structure	evidence	BlCel5B Crystal Structure	RESULTS
+0	7	BlCel5B	protein	BlCel5B crystals in the substrate-free form and complexed with cellopentaose (C5) were obtained and diffracted to 1.7 Å and 1.75 Å resolutions, respectively (Supplementary Table 1).	RESULTS
+8	16	crystals	evidence	BlCel5B crystals in the substrate-free form and complexed with cellopentaose (C5) were obtained and diffracted to 1.7 Å and 1.75 Å resolutions, respectively (Supplementary Table 1).	RESULTS
+24	38	substrate-free	protein_state	BlCel5B crystals in the substrate-free form and complexed with cellopentaose (C5) were obtained and diffracted to 1.7 Å and 1.75 Å resolutions, respectively (Supplementary Table 1).	RESULTS
+48	62	complexed with	protein_state	BlCel5B crystals in the substrate-free form and complexed with cellopentaose (C5) were obtained and diffracted to 1.7 Å and 1.75 Å resolutions, respectively (Supplementary Table 1).	RESULTS
+63	76	cellopentaose	chemical	BlCel5B crystals in the substrate-free form and complexed with cellopentaose (C5) were obtained and diffracted to 1.7 Å and 1.75 Å resolutions, respectively (Supplementary Table 1).	RESULTS
+78	80	C5	chemical	BlCel5B crystals in the substrate-free form and complexed with cellopentaose (C5) were obtained and diffracted to 1.7 Å and 1.75 Å resolutions, respectively (Supplementary Table 1).	RESULTS
+4	18	substrate-free	protein_state	The substrate-free and complexed structures exhibited no substantial conformational differences (with the exception of the substrate).	RESULTS
+23	32	complexed	protein_state	The substrate-free and complexed structures exhibited no substantial conformational differences (with the exception of the substrate).	RESULTS
+33	43	structures	evidence	The substrate-free and complexed structures exhibited no substantial conformational differences (with the exception of the substrate).	RESULTS
+35	40	loops	structure_element	Because of minor variations in the loops located distal to the substrate-binding site, a root mean squared deviation (rmsd) of 0.33 Å between the complexed and substrate-free structures was observed.	RESULTS
+63	85	substrate-binding site	site	Because of minor variations in the loops located distal to the substrate-binding site, a root mean squared deviation (rmsd) of 0.33 Å between the complexed and substrate-free structures was observed.	RESULTS
+89	116	root mean squared deviation	evidence	Because of minor variations in the loops located distal to the substrate-binding site, a root mean squared deviation (rmsd) of 0.33 Å between the complexed and substrate-free structures was observed.	RESULTS
+118	122	rmsd	evidence	Because of minor variations in the loops located distal to the substrate-binding site, a root mean squared deviation (rmsd) of 0.33 Å between the complexed and substrate-free structures was observed.	RESULTS
+146	155	complexed	protein_state	Because of minor variations in the loops located distal to the substrate-binding site, a root mean squared deviation (rmsd) of 0.33 Å between the complexed and substrate-free structures was observed.	RESULTS
+160	174	substrate-free	protein_state	Because of minor variations in the loops located distal to the substrate-binding site, a root mean squared deviation (rmsd) of 0.33 Å between the complexed and substrate-free structures was observed.	RESULTS
+175	185	structures	evidence	Because of minor variations in the loops located distal to the substrate-binding site, a root mean squared deviation (rmsd) of 0.33 Å between the complexed and substrate-free structures was observed.	RESULTS
+116	133	first 17 residues	residue_range	A single protein chain occupies the asymmetric unit, and most of the residues were built, with the exception of the first 17 residues and those in the loop between L398 and P405 due to weak electron density.	RESULTS
+151	155	loop	structure_element	A single protein chain occupies the asymmetric unit, and most of the residues were built, with the exception of the first 17 residues and those in the loop between L398 and P405 due to weak electron density.	RESULTS
+164	168	L398	residue_name_number	A single protein chain occupies the asymmetric unit, and most of the residues were built, with the exception of the first 17 residues and those in the loop between L398 and P405 due to weak electron density.	RESULTS
+173	177	P405	residue_name_number	A single protein chain occupies the asymmetric unit, and most of the residues were built, with the exception of the first 17 residues and those in the loop between L398 and P405 due to weak electron density.	RESULTS
+190	206	electron density	evidence	A single protein chain occupies the asymmetric unit, and most of the residues were built, with the exception of the first 17 residues and those in the loop between L398 and P405 due to weak electron density.	RESULTS
+4	11	BlCel5B	protein	The BlCel5B structure comprises three distinct domains: an N-terminal CD (residues 18 to 330), an Ig-like module (residues 335 to 428) and a family 46 CBM (residues 432 to 533) (Fig. 1A,B).	RESULTS
+12	21	structure	evidence	The BlCel5B structure comprises three distinct domains: an N-terminal CD (residues 18 to 330), an Ig-like module (residues 335 to 428) and a family 46 CBM (residues 432 to 533) (Fig. 1A,B).	RESULTS
+70	72	CD	structure_element	The BlCel5B structure comprises three distinct domains: an N-terminal CD (residues 18 to 330), an Ig-like module (residues 335 to 428) and a family 46 CBM (residues 432 to 533) (Fig. 1A,B).	RESULTS
+83	92	18 to 330	residue_range	The BlCel5B structure comprises three distinct domains: an N-terminal CD (residues 18 to 330), an Ig-like module (residues 335 to 428) and a family 46 CBM (residues 432 to 533) (Fig. 1A,B).	RESULTS
+98	112	Ig-like module	structure_element	The BlCel5B structure comprises three distinct domains: an N-terminal CD (residues 18 to 330), an Ig-like module (residues 335 to 428) and a family 46 CBM (residues 432 to 533) (Fig. 1A,B).	RESULTS
+123	133	335 to 428	residue_range	The BlCel5B structure comprises three distinct domains: an N-terminal CD (residues 18 to 330), an Ig-like module (residues 335 to 428) and a family 46 CBM (residues 432 to 533) (Fig. 1A,B).	RESULTS
+141	154	family 46 CBM	structure_element	The BlCel5B structure comprises three distinct domains: an N-terminal CD (residues 18 to 330), an Ig-like module (residues 335 to 428) and a family 46 CBM (residues 432 to 533) (Fig. 1A,B).	RESULTS
+165	175	432 to 533	residue_range	The BlCel5B structure comprises three distinct domains: an N-terminal CD (residues 18 to 330), an Ig-like module (residues 335 to 428) and a family 46 CBM (residues 432 to 533) (Fig. 1A,B).	RESULTS
+34	37	GH5	protein_type	Similarly to other members of the GH5 family, the CD of BlCel5B has a typical TIM barrel fold with eight inner β-strands and eight outer α helices that are interconnected by loops and three short α helices.	RESULTS
+50	52	CD	structure_element	Similarly to other members of the GH5 family, the CD of BlCel5B has a typical TIM barrel fold with eight inner β-strands and eight outer α helices that are interconnected by loops and three short α helices.	RESULTS
+56	63	BlCel5B	protein	Similarly to other members of the GH5 family, the CD of BlCel5B has a typical TIM barrel fold with eight inner β-strands and eight outer α helices that are interconnected by loops and three short α helices.	RESULTS
+78	93	TIM barrel fold	structure_element	Similarly to other members of the GH5 family, the CD of BlCel5B has a typical TIM barrel fold with eight inner β-strands and eight outer α helices that are interconnected by loops and three short α helices.	RESULTS
+111	120	β-strands	structure_element	Similarly to other members of the GH5 family, the CD of BlCel5B has a typical TIM barrel fold with eight inner β-strands and eight outer α helices that are interconnected by loops and three short α helices.	RESULTS
+137	146	α helices	structure_element	Similarly to other members of the GH5 family, the CD of BlCel5B has a typical TIM barrel fold with eight inner β-strands and eight outer α helices that are interconnected by loops and three short α helices.	RESULTS
+174	179	loops	structure_element	Similarly to other members of the GH5 family, the CD of BlCel5B has a typical TIM barrel fold with eight inner β-strands and eight outer α helices that are interconnected by loops and three short α helices.	RESULTS
+196	205	α helices	structure_element	Similarly to other members of the GH5 family, the CD of BlCel5B has a typical TIM barrel fold with eight inner β-strands and eight outer α helices that are interconnected by loops and three short α helices.	RESULTS
+11	18	linkers	structure_element	Very short linkers, D429-D430-P431 and V331-P332-N333-A334, connect the CBM46 to the Ig-like module and the Ig-like module to the CD, respectively.	RESULTS
+20	34	D429-D430-P431	structure_element	Very short linkers, D429-D430-P431 and V331-P332-N333-A334, connect the CBM46 to the Ig-like module and the Ig-like module to the CD, respectively.	RESULTS
+39	58	V331-P332-N333-A334	structure_element	Very short linkers, D429-D430-P431 and V331-P332-N333-A334, connect the CBM46 to the Ig-like module and the Ig-like module to the CD, respectively.	RESULTS
+72	77	CBM46	structure_element	Very short linkers, D429-D430-P431 and V331-P332-N333-A334, connect the CBM46 to the Ig-like module and the Ig-like module to the CD, respectively.	RESULTS
+85	99	Ig-like module	structure_element	Very short linkers, D429-D430-P431 and V331-P332-N333-A334, connect the CBM46 to the Ig-like module and the Ig-like module to the CD, respectively.	RESULTS
+108	122	Ig-like module	structure_element	Very short linkers, D429-D430-P431 and V331-P332-N333-A334, connect the CBM46 to the Ig-like module and the Ig-like module to the CD, respectively.	RESULTS
+130	132	CD	structure_element	Very short linkers, D429-D430-P431 and V331-P332-N333-A334, connect the CBM46 to the Ig-like module and the Ig-like module to the CD, respectively.	RESULTS
+5	19	Ig-like module	structure_element	Both Ig-like module and CBM46 have a β-sandwich fold composed of two β-sheets of four and three antiparallel β-strands interconnected by loops and a short α helix between strands β3 and β4 (Fig. 1C).	RESULTS
+24	29	CBM46	structure_element	Both Ig-like module and CBM46 have a β-sandwich fold composed of two β-sheets of four and three antiparallel β-strands interconnected by loops and a short α helix between strands β3 and β4 (Fig. 1C).	RESULTS
+37	52	β-sandwich fold	structure_element	Both Ig-like module and CBM46 have a β-sandwich fold composed of two β-sheets of four and three antiparallel β-strands interconnected by loops and a short α helix between strands β3 and β4 (Fig. 1C).	RESULTS
+69	77	β-sheets	structure_element	Both Ig-like module and CBM46 have a β-sandwich fold composed of two β-sheets of four and three antiparallel β-strands interconnected by loops and a short α helix between strands β3 and β4 (Fig. 1C).	RESULTS
+96	118	antiparallel β-strands	structure_element	Both Ig-like module and CBM46 have a β-sandwich fold composed of two β-sheets of four and three antiparallel β-strands interconnected by loops and a short α helix between strands β3 and β4 (Fig. 1C).	RESULTS
+137	142	loops	structure_element	Both Ig-like module and CBM46 have a β-sandwich fold composed of two β-sheets of four and three antiparallel β-strands interconnected by loops and a short α helix between strands β3 and β4 (Fig. 1C).	RESULTS
+155	162	α helix	structure_element	Both Ig-like module and CBM46 have a β-sandwich fold composed of two β-sheets of four and three antiparallel β-strands interconnected by loops and a short α helix between strands β3 and β4 (Fig. 1C).	RESULTS
+171	178	strands	structure_element	Both Ig-like module and CBM46 have a β-sandwich fold composed of two β-sheets of four and three antiparallel β-strands interconnected by loops and a short α helix between strands β3 and β4 (Fig. 1C).	RESULTS
+179	181	β3	structure_element	Both Ig-like module and CBM46 have a β-sandwich fold composed of two β-sheets of four and three antiparallel β-strands interconnected by loops and a short α helix between strands β3 and β4 (Fig. 1C).	RESULTS
+186	188	β4	structure_element	Both Ig-like module and CBM46 have a β-sandwich fold composed of two β-sheets of four and three antiparallel β-strands interconnected by loops and a short α helix between strands β3 and β4 (Fig. 1C).	RESULTS
+2	23	structural comparison	experimental_method	A structural comparison between the Ig-like module and the CBM46 using the Dali server yielded an rmsd of 2.3 Å and a Z-score of 10.2.	RESULTS
+36	50	Ig-like module	structure_element	A structural comparison between the Ig-like module and the CBM46 using the Dali server yielded an rmsd of 2.3 Å and a Z-score of 10.2.	RESULTS
+59	64	CBM46	structure_element	A structural comparison between the Ig-like module and the CBM46 using the Dali server yielded an rmsd of 2.3 Å and a Z-score of 10.2.	RESULTS
+75	86	Dali server	experimental_method	A structural comparison between the Ig-like module and the CBM46 using the Dali server yielded an rmsd of 2.3 Å and a Z-score of 10.2.	RESULTS
+98	102	rmsd	evidence	A structural comparison between the Ig-like module and the CBM46 using the Dali server yielded an rmsd of 2.3 Å and a Z-score of 10.2.	RESULTS
+118	125	Z-score	evidence	A structural comparison between the Ig-like module and the CBM46 using the Dali server yielded an rmsd of 2.3 Å and a Z-score of 10.2.	RESULTS
+2	24	structure-based search	experimental_method	A structure-based search performed using the same server showed that the Ig-like module is similar to the Ig-like module from a recently solved crystal structure of a tri-modular GH5_4 enzyme from Bacillus halodurans, BhCel5B, with rmsd = 1.3 Å and Z-score = 15.3.	RESULTS
+73	87	Ig-like module	structure_element	A structure-based search performed using the same server showed that the Ig-like module is similar to the Ig-like module from a recently solved crystal structure of a tri-modular GH5_4 enzyme from Bacillus halodurans, BhCel5B, with rmsd = 1.3 Å and Z-score = 15.3.	RESULTS
+106	120	Ig-like module	structure_element	A structure-based search performed using the same server showed that the Ig-like module is similar to the Ig-like module from a recently solved crystal structure of a tri-modular GH5_4 enzyme from Bacillus halodurans, BhCel5B, with rmsd = 1.3 Å and Z-score = 15.3.	RESULTS
+137	143	solved	experimental_method	A structure-based search performed using the same server showed that the Ig-like module is similar to the Ig-like module from a recently solved crystal structure of a tri-modular GH5_4 enzyme from Bacillus halodurans, BhCel5B, with rmsd = 1.3 Å and Z-score = 15.3.	RESULTS
+144	161	crystal structure	evidence	A structure-based search performed using the same server showed that the Ig-like module is similar to the Ig-like module from a recently solved crystal structure of a tri-modular GH5_4 enzyme from Bacillus halodurans, BhCel5B, with rmsd = 1.3 Å and Z-score = 15.3.	RESULTS
+167	178	tri-modular	structure_element	A structure-based search performed using the same server showed that the Ig-like module is similar to the Ig-like module from a recently solved crystal structure of a tri-modular GH5_4 enzyme from Bacillus halodurans, BhCel5B, with rmsd = 1.3 Å and Z-score = 15.3.	RESULTS
+179	184	GH5_4	protein_type	A structure-based search performed using the same server showed that the Ig-like module is similar to the Ig-like module from a recently solved crystal structure of a tri-modular GH5_4 enzyme from Bacillus halodurans, BhCel5B, with rmsd = 1.3 Å and Z-score = 15.3.	RESULTS
+197	216	Bacillus halodurans	species	A structure-based search performed using the same server showed that the Ig-like module is similar to the Ig-like module from a recently solved crystal structure of a tri-modular GH5_4 enzyme from Bacillus halodurans, BhCel5B, with rmsd = 1.3 Å and Z-score = 15.3.	RESULTS
+218	225	BhCel5B	protein	A structure-based search performed using the same server showed that the Ig-like module is similar to the Ig-like module from a recently solved crystal structure of a tri-modular GH5_4 enzyme from Bacillus halodurans, BhCel5B, with rmsd = 1.3 Å and Z-score = 15.3.	RESULTS
+232	236	rmsd	evidence	A structure-based search performed using the same server showed that the Ig-like module is similar to the Ig-like module from a recently solved crystal structure of a tri-modular GH5_4 enzyme from Bacillus halodurans, BhCel5B, with rmsd = 1.3 Å and Z-score = 15.3.	RESULTS
+249	256	Z-score	evidence	A structure-based search performed using the same server showed that the Ig-like module is similar to the Ig-like module from a recently solved crystal structure of a tri-modular GH5_4 enzyme from Bacillus halodurans, BhCel5B, with rmsd = 1.3 Å and Z-score = 15.3.	RESULTS
+4	9	CBM46	structure_element	The CBM46 from BhCel5B is the most structurally similar to BlCel5B CBM46, with rmsd = 1.6 Å and Z-score = 12.4.	RESULTS
+15	22	BhCel5B	protein	The CBM46 from BhCel5B is the most structurally similar to BlCel5B CBM46, with rmsd = 1.6 Å and Z-score = 12.4.	RESULTS
+59	66	BlCel5B	protein	The CBM46 from BhCel5B is the most structurally similar to BlCel5B CBM46, with rmsd = 1.6 Å and Z-score = 12.4.	RESULTS
+67	72	CBM46	structure_element	The CBM46 from BhCel5B is the most structurally similar to BlCel5B CBM46, with rmsd = 1.6 Å and Z-score = 12.4.	RESULTS
+79	83	rmsd	evidence	The CBM46 from BhCel5B is the most structurally similar to BlCel5B CBM46, with rmsd = 1.6 Å and Z-score = 12.4.	RESULTS
+96	103	Z-score	evidence	The CBM46 from BhCel5B is the most structurally similar to BlCel5B CBM46, with rmsd = 1.6 Å and Z-score = 12.4.	RESULTS
+34	41	BhCel5B	protein	The sequence identity relative to BhCel5B, however, is low (28% for Ig-like and 25% for CBM46).	RESULTS
+68	75	Ig-like	structure_element	The sequence identity relative to BhCel5B, however, is low (28% for Ig-like and 25% for CBM46).	RESULTS
+88	93	CBM46	structure_element	The sequence identity relative to BhCel5B, however, is low (28% for Ig-like and 25% for CBM46).	RESULTS
+4	18	Ig-like module	structure_element	The Ig-like module, adjacent to the CD, contains only one tyrosine (Y367) exposed to solvent and no tryptophan residues.	RESULTS
+36	38	CD	structure_element	The Ig-like module, adjacent to the CD, contains only one tyrosine (Y367) exposed to solvent and no tryptophan residues.	RESULTS
+58	66	tyrosine	residue_name	The Ig-like module, adjacent to the CD, contains only one tyrosine (Y367) exposed to solvent and no tryptophan residues.	RESULTS
+68	72	Y367	residue_name_number	The Ig-like module, adjacent to the CD, contains only one tyrosine (Y367) exposed to solvent and no tryptophan residues.	RESULTS
+100	110	tryptophan	residue_name	The Ig-like module, adjacent to the CD, contains only one tyrosine (Y367) exposed to solvent and no tryptophan residues.	RESULTS
+47	54	glucose	chemical	Because aromatic residues play a major role in glucose recognition, this observation suggests that substrate binding may not be the primary function of Ig-like module.	RESULTS
+152	166	Ig-like module	structure_element	Because aromatic residues play a major role in glucose recognition, this observation suggests that substrate binding may not be the primary function of Ig-like module.	RESULTS
+17	22	CBM46	structure_element	In contrast, the CBM46 has three tryptophan residues, two of which face the CD substrate binding site (Fig. 1A), indicating that it may be actively engaged in the carbohydrate binding.	RESULTS
+33	43	tryptophan	residue_name	In contrast, the CBM46 has three tryptophan residues, two of which face the CD substrate binding site (Fig. 1A), indicating that it may be actively engaged in the carbohydrate binding.	RESULTS
+76	78	CD	structure_element	In contrast, the CBM46 has three tryptophan residues, two of which face the CD substrate binding site (Fig. 1A), indicating that it may be actively engaged in the carbohydrate binding.	RESULTS
+79	101	substrate binding site	site	In contrast, the CBM46 has three tryptophan residues, two of which face the CD substrate binding site (Fig. 1A), indicating that it may be actively engaged in the carbohydrate binding.	RESULTS
+163	175	carbohydrate	chemical	In contrast, the CBM46 has three tryptophan residues, two of which face the CD substrate binding site (Fig. 1A), indicating that it may be actively engaged in the carbohydrate binding.	RESULTS
+0	21	Electron density maps	evidence	Electron density maps clearly reveal the presence of a cellotetraose (C4) and not a soaked cellopentaose (C5) in the CD negative substrate-binding subsites (Fig. 1D), indicating that BlCel5B is catalytically active in the crystal state and able to cleave a C5 molecule.	RESULTS
+41	52	presence of	protein_state	Electron density maps clearly reveal the presence of a cellotetraose (C4) and not a soaked cellopentaose (C5) in the CD negative substrate-binding subsites (Fig. 1D), indicating that BlCel5B is catalytically active in the crystal state and able to cleave a C5 molecule.	RESULTS
+55	68	cellotetraose	chemical	Electron density maps clearly reveal the presence of a cellotetraose (C4) and not a soaked cellopentaose (C5) in the CD negative substrate-binding subsites (Fig. 1D), indicating that BlCel5B is catalytically active in the crystal state and able to cleave a C5 molecule.	RESULTS
+70	72	C4	chemical	Electron density maps clearly reveal the presence of a cellotetraose (C4) and not a soaked cellopentaose (C5) in the CD negative substrate-binding subsites (Fig. 1D), indicating that BlCel5B is catalytically active in the crystal state and able to cleave a C5 molecule.	RESULTS
+91	104	cellopentaose	chemical	Electron density maps clearly reveal the presence of a cellotetraose (C4) and not a soaked cellopentaose (C5) in the CD negative substrate-binding subsites (Fig. 1D), indicating that BlCel5B is catalytically active in the crystal state and able to cleave a C5 molecule.	RESULTS
+106	108	C5	chemical	Electron density maps clearly reveal the presence of a cellotetraose (C4) and not a soaked cellopentaose (C5) in the CD negative substrate-binding subsites (Fig. 1D), indicating that BlCel5B is catalytically active in the crystal state and able to cleave a C5 molecule.	RESULTS
+117	119	CD	structure_element	Electron density maps clearly reveal the presence of a cellotetraose (C4) and not a soaked cellopentaose (C5) in the CD negative substrate-binding subsites (Fig. 1D), indicating that BlCel5B is catalytically active in the crystal state and able to cleave a C5 molecule.	RESULTS
+120	155	negative substrate-binding subsites	site	Electron density maps clearly reveal the presence of a cellotetraose (C4) and not a soaked cellopentaose (C5) in the CD negative substrate-binding subsites (Fig. 1D), indicating that BlCel5B is catalytically active in the crystal state and able to cleave a C5 molecule.	RESULTS
+183	190	BlCel5B	protein	Electron density maps clearly reveal the presence of a cellotetraose (C4) and not a soaked cellopentaose (C5) in the CD negative substrate-binding subsites (Fig. 1D), indicating that BlCel5B is catalytically active in the crystal state and able to cleave a C5 molecule.	RESULTS
+194	214	catalytically active	protein_state	Electron density maps clearly reveal the presence of a cellotetraose (C4) and not a soaked cellopentaose (C5) in the CD negative substrate-binding subsites (Fig. 1D), indicating that BlCel5B is catalytically active in the crystal state and able to cleave a C5 molecule.	RESULTS
+257	259	C5	chemical	Electron density maps clearly reveal the presence of a cellotetraose (C4) and not a soaked cellopentaose (C5) in the CD negative substrate-binding subsites (Fig. 1D), indicating that BlCel5B is catalytically active in the crystal state and able to cleave a C5 molecule.	RESULTS
+4	28	lack of electron density	evidence	The lack of electron density verifies the absence of the fifth glucose moiety from the soaked C5, and a closer inspection of the structure confirmed that the presence of a fifth glucose unit would be sterically hindered by the catalytic residues on the reducing end and by residue R234 of a symmetry-related enzyme molecule on the non-reducing end.	RESULTS
+42	52	absence of	protein_state	The lack of electron density verifies the absence of the fifth glucose moiety from the soaked C5, and a closer inspection of the structure confirmed that the presence of a fifth glucose unit would be sterically hindered by the catalytic residues on the reducing end and by residue R234 of a symmetry-related enzyme molecule on the non-reducing end.	RESULTS
+57	62	fifth	residue_number	The lack of electron density verifies the absence of the fifth glucose moiety from the soaked C5, and a closer inspection of the structure confirmed that the presence of a fifth glucose unit would be sterically hindered by the catalytic residues on the reducing end and by residue R234 of a symmetry-related enzyme molecule on the non-reducing end.	RESULTS
+63	70	glucose	chemical	The lack of electron density verifies the absence of the fifth glucose moiety from the soaked C5, and a closer inspection of the structure confirmed that the presence of a fifth glucose unit would be sterically hindered by the catalytic residues on the reducing end and by residue R234 of a symmetry-related enzyme molecule on the non-reducing end.	RESULTS
+94	96	C5	chemical	The lack of electron density verifies the absence of the fifth glucose moiety from the soaked C5, and a closer inspection of the structure confirmed that the presence of a fifth glucose unit would be sterically hindered by the catalytic residues on the reducing end and by residue R234 of a symmetry-related enzyme molecule on the non-reducing end.	RESULTS
+129	138	structure	evidence	The lack of electron density verifies the absence of the fifth glucose moiety from the soaked C5, and a closer inspection of the structure confirmed that the presence of a fifth glucose unit would be sterically hindered by the catalytic residues on the reducing end and by residue R234 of a symmetry-related enzyme molecule on the non-reducing end.	RESULTS
+158	169	presence of	protein_state	The lack of electron density verifies the absence of the fifth glucose moiety from the soaked C5, and a closer inspection of the structure confirmed that the presence of a fifth glucose unit would be sterically hindered by the catalytic residues on the reducing end and by residue R234 of a symmetry-related enzyme molecule on the non-reducing end.	RESULTS
+172	177	fifth	residue_number	The lack of electron density verifies the absence of the fifth glucose moiety from the soaked C5, and a closer inspection of the structure confirmed that the presence of a fifth glucose unit would be sterically hindered by the catalytic residues on the reducing end and by residue R234 of a symmetry-related enzyme molecule on the non-reducing end.	RESULTS
+178	185	glucose	chemical	The lack of electron density verifies the absence of the fifth glucose moiety from the soaked C5, and a closer inspection of the structure confirmed that the presence of a fifth glucose unit would be sterically hindered by the catalytic residues on the reducing end and by residue R234 of a symmetry-related enzyme molecule on the non-reducing end.	RESULTS
+227	245	catalytic residues	site	The lack of electron density verifies the absence of the fifth glucose moiety from the soaked C5, and a closer inspection of the structure confirmed that the presence of a fifth glucose unit would be sterically hindered by the catalytic residues on the reducing end and by residue R234 of a symmetry-related enzyme molecule on the non-reducing end.	RESULTS
+281	285	R234	residue_name_number	The lack of electron density verifies the absence of the fifth glucose moiety from the soaked C5, and a closer inspection of the structure confirmed that the presence of a fifth glucose unit would be sterically hindered by the catalytic residues on the reducing end and by residue R234 of a symmetry-related enzyme molecule on the non-reducing end.	RESULTS
+15	22	BlCel5B	protein	The ability of BlCel5B to cleave C5 into glucose and C4 molecules in solution was demonstrated by enzymatic product profile mass spectrometry analysis (Fig. 2A).	RESULTS
+33	35	C5	chemical	The ability of BlCel5B to cleave C5 into glucose and C4 molecules in solution was demonstrated by enzymatic product profile mass spectrometry analysis (Fig. 2A).	RESULTS
+41	48	glucose	chemical	The ability of BlCel5B to cleave C5 into glucose and C4 molecules in solution was demonstrated by enzymatic product profile mass spectrometry analysis (Fig. 2A).	RESULTS
+53	55	C4	chemical	The ability of BlCel5B to cleave C5 into glucose and C4 molecules in solution was demonstrated by enzymatic product profile mass spectrometry analysis (Fig. 2A).	RESULTS
+98	141	enzymatic product profile mass spectrometry	experimental_method	The ability of BlCel5B to cleave C5 into glucose and C4 molecules in solution was demonstrated by enzymatic product profile mass spectrometry analysis (Fig. 2A).	RESULTS
+4	6	C4	chemical	The C4 oligomer in the BlCel5B binding site is coordinated by hydrogen bonds to residues N36, H113, H114, N158, W301, and N303 and by a CH-π interaction with residue W47 (Fig. 1D).	RESULTS
+23	30	BlCel5B	protein	The C4 oligomer in the BlCel5B binding site is coordinated by hydrogen bonds to residues N36, H113, H114, N158, W301, and N303 and by a CH-π interaction with residue W47 (Fig. 1D).	RESULTS
+31	43	binding site	site	The C4 oligomer in the BlCel5B binding site is coordinated by hydrogen bonds to residues N36, H113, H114, N158, W301, and N303 and by a CH-π interaction with residue W47 (Fig. 1D).	RESULTS
+47	58	coordinated	bond_interaction	The C4 oligomer in the BlCel5B binding site is coordinated by hydrogen bonds to residues N36, H113, H114, N158, W301, and N303 and by a CH-π interaction with residue W47 (Fig. 1D).	RESULTS
+62	76	hydrogen bonds	bond_interaction	The C4 oligomer in the BlCel5B binding site is coordinated by hydrogen bonds to residues N36, H113, H114, N158, W301, and N303 and by a CH-π interaction with residue W47 (Fig. 1D).	RESULTS
+89	92	N36	residue_name_number	The C4 oligomer in the BlCel5B binding site is coordinated by hydrogen bonds to residues N36, H113, H114, N158, W301, and N303 and by a CH-π interaction with residue W47 (Fig. 1D).	RESULTS
+94	98	H113	residue_name_number	The C4 oligomer in the BlCel5B binding site is coordinated by hydrogen bonds to residues N36, H113, H114, N158, W301, and N303 and by a CH-π interaction with residue W47 (Fig. 1D).	RESULTS
+100	104	H114	residue_name_number	The C4 oligomer in the BlCel5B binding site is coordinated by hydrogen bonds to residues N36, H113, H114, N158, W301, and N303 and by a CH-π interaction with residue W47 (Fig. 1D).	RESULTS
+106	110	N158	residue_name_number	The C4 oligomer in the BlCel5B binding site is coordinated by hydrogen bonds to residues N36, H113, H114, N158, W301, and N303 and by a CH-π interaction with residue W47 (Fig. 1D).	RESULTS
+112	116	W301	residue_name_number	The C4 oligomer in the BlCel5B binding site is coordinated by hydrogen bonds to residues N36, H113, H114, N158, W301, and N303 and by a CH-π interaction with residue W47 (Fig. 1D).	RESULTS
+122	126	N303	residue_name_number	The C4 oligomer in the BlCel5B binding site is coordinated by hydrogen bonds to residues N36, H113, H114, N158, W301, and N303 and by a CH-π interaction with residue W47 (Fig. 1D).	RESULTS
+136	152	CH-π interaction	bond_interaction	The C4 oligomer in the BlCel5B binding site is coordinated by hydrogen bonds to residues N36, H113, H114, N158, W301, and N303 and by a CH-π interaction with residue W47 (Fig. 1D).	RESULTS
+166	169	W47	residue_name_number	The C4 oligomer in the BlCel5B binding site is coordinated by hydrogen bonds to residues N36, H113, H114, N158, W301, and N303 and by a CH-π interaction with residue W47 (Fig. 1D).	RESULTS
+29	31	CD	structure_element	These residues belong to the CD and are conserved in the GH5 family.	RESULTS
+40	49	conserved	protein_state	These residues belong to the CD and are conserved in the GH5 family.	RESULTS
+57	60	GH5	protein_type	These residues belong to the CD and are conserved in the GH5 family.	RESULTS
+0	7	BlCel5B	protein	BlCel5B enzymatic activity	RESULTS
+0	7	BlCel5B	protein	BlCel5B exhibits optimum activity toward carboxymethylcellulose (CMC; 8.7 U/mg) at a pH of 4.0 and 55 °C and retains approximately half of its maximum activity at 80 °C, demonstrating considerable thermal stability (Fig. 2B,C).	RESULTS
+41	63	carboxymethylcellulose	chemical	BlCel5B exhibits optimum activity toward carboxymethylcellulose (CMC; 8.7 U/mg) at a pH of 4.0 and 55 °C and retains approximately half of its maximum activity at 80 °C, demonstrating considerable thermal stability (Fig. 2B,C).	RESULTS
+65	68	CMC	chemical	BlCel5B exhibits optimum activity toward carboxymethylcellulose (CMC; 8.7 U/mg) at a pH of 4.0 and 55 °C and retains approximately half of its maximum activity at 80 °C, demonstrating considerable thermal stability (Fig. 2B,C).	RESULTS
+0	7	BlCel5B	protein	BlCel5B is also active on β-glucan (34 U/mg), lichenan (17.8 U/mg) and xyloglucan (15.7 U/mg) substrates (Table 1), whereas no activity was detected on galactomannan, rye arabinoxylan, 1,4-β-mannan or the insoluble substrate Azo-Avicel.	RESULTS
+16	22	active	protein_state	BlCel5B is also active on β-glucan (34 U/mg), lichenan (17.8 U/mg) and xyloglucan (15.7 U/mg) substrates (Table 1), whereas no activity was detected on galactomannan, rye arabinoxylan, 1,4-β-mannan or the insoluble substrate Azo-Avicel.	RESULTS
+26	34	β-glucan	chemical	BlCel5B is also active on β-glucan (34 U/mg), lichenan (17.8 U/mg) and xyloglucan (15.7 U/mg) substrates (Table 1), whereas no activity was detected on galactomannan, rye arabinoxylan, 1,4-β-mannan or the insoluble substrate Azo-Avicel.	RESULTS
+46	54	lichenan	chemical	BlCel5B is also active on β-glucan (34 U/mg), lichenan (17.8 U/mg) and xyloglucan (15.7 U/mg) substrates (Table 1), whereas no activity was detected on galactomannan, rye arabinoxylan, 1,4-β-mannan or the insoluble substrate Azo-Avicel.	RESULTS
+71	81	xyloglucan	chemical	BlCel5B is also active on β-glucan (34 U/mg), lichenan (17.8 U/mg) and xyloglucan (15.7 U/mg) substrates (Table 1), whereas no activity was detected on galactomannan, rye arabinoxylan, 1,4-β-mannan or the insoluble substrate Azo-Avicel.	RESULTS
+152	165	galactomannan	chemical	BlCel5B is also active on β-glucan (34 U/mg), lichenan (17.8 U/mg) and xyloglucan (15.7 U/mg) substrates (Table 1), whereas no activity was detected on galactomannan, rye arabinoxylan, 1,4-β-mannan or the insoluble substrate Azo-Avicel.	RESULTS
+167	170	rye	taxonomy_domain	BlCel5B is also active on β-glucan (34 U/mg), lichenan (17.8 U/mg) and xyloglucan (15.7 U/mg) substrates (Table 1), whereas no activity was detected on galactomannan, rye arabinoxylan, 1,4-β-mannan or the insoluble substrate Azo-Avicel.	RESULTS
+171	183	arabinoxylan	chemical	BlCel5B is also active on β-glucan (34 U/mg), lichenan (17.8 U/mg) and xyloglucan (15.7 U/mg) substrates (Table 1), whereas no activity was detected on galactomannan, rye arabinoxylan, 1,4-β-mannan or the insoluble substrate Azo-Avicel.	RESULTS
+185	197	1,4-β-mannan	chemical	BlCel5B is also active on β-glucan (34 U/mg), lichenan (17.8 U/mg) and xyloglucan (15.7 U/mg) substrates (Table 1), whereas no activity was detected on galactomannan, rye arabinoxylan, 1,4-β-mannan or the insoluble substrate Azo-Avicel.	RESULTS
+225	235	Azo-Avicel	chemical	BlCel5B is also active on β-glucan (34 U/mg), lichenan (17.8 U/mg) and xyloglucan (15.7 U/mg) substrates (Table 1), whereas no activity was detected on galactomannan, rye arabinoxylan, 1,4-β-mannan or the insoluble substrate Azo-Avicel.	RESULTS
+44	69	Michaelis-Menten behavior	experimental_method	Kinetic parameters were calculated assuming Michaelis-Menten behavior with CMC as substrate: KM = 1.78 g L−1 and Vmax = 1.41 × 10−4 g s−1 mg protein−1 (Fig. 2D).	RESULTS
+75	78	CMC	chemical	Kinetic parameters were calculated assuming Michaelis-Menten behavior with CMC as substrate: KM = 1.78 g L−1 and Vmax = 1.41 × 10−4 g s−1 mg protein−1 (Fig. 2D).	RESULTS
+93	95	KM	evidence	Kinetic parameters were calculated assuming Michaelis-Menten behavior with CMC as substrate: KM = 1.78 g L−1 and Vmax = 1.41 × 10−4 g s−1 mg protein−1 (Fig. 2D).	RESULTS
+113	117	Vmax	evidence	Kinetic parameters were calculated assuming Michaelis-Menten behavior with CMC as substrate: KM = 1.78 g L−1 and Vmax = 1.41 × 10−4 g s−1 mg protein−1 (Fig. 2D).	RESULTS
+9	16	BlCel5B	protein	Although BlCel5B is not a highly active enzyme against one specific substrate as compared to others GH5_4, it has the advantage of being active against different substrates with β-1,3 and/or β-1,4 glycosidic linkages.	RESULTS
+33	39	active	protein_state	Although BlCel5B is not a highly active enzyme against one specific substrate as compared to others GH5_4, it has the advantage of being active against different substrates with β-1,3 and/or β-1,4 glycosidic linkages.	RESULTS
+100	105	GH5_4	protein_type	Although BlCel5B is not a highly active enzyme against one specific substrate as compared to others GH5_4, it has the advantage of being active against different substrates with β-1,3 and/or β-1,4 glycosidic linkages.	RESULTS
+137	143	active	protein_state	Although BlCel5B is not a highly active enzyme against one specific substrate as compared to others GH5_4, it has the advantage of being active against different substrates with β-1,3 and/or β-1,4 glycosidic linkages.	RESULTS
+36	53	ancillary modules	structure_element	To understand the importance of the ancillary modules for BlCel5B activity, enzymatic assays were carried out using four enzyme mutants: a CBM46 deletion (ΔCBM46) and an Ig-like + CBM46 deletion (ΔIg-CBM46) as well as point mutations of the CBM46 inner surface residues W479A and W481A.	RESULTS
+58	65	BlCel5B	protein	To understand the importance of the ancillary modules for BlCel5B activity, enzymatic assays were carried out using four enzyme mutants: a CBM46 deletion (ΔCBM46) and an Ig-like + CBM46 deletion (ΔIg-CBM46) as well as point mutations of the CBM46 inner surface residues W479A and W481A.	RESULTS
+76	92	enzymatic assays	experimental_method	To understand the importance of the ancillary modules for BlCel5B activity, enzymatic assays were carried out using four enzyme mutants: a CBM46 deletion (ΔCBM46) and an Ig-like + CBM46 deletion (ΔIg-CBM46) as well as point mutations of the CBM46 inner surface residues W479A and W481A.	RESULTS
+128	135	mutants	protein_state	To understand the importance of the ancillary modules for BlCel5B activity, enzymatic assays were carried out using four enzyme mutants: a CBM46 deletion (ΔCBM46) and an Ig-like + CBM46 deletion (ΔIg-CBM46) as well as point mutations of the CBM46 inner surface residues W479A and W481A.	RESULTS
+139	144	CBM46	structure_element	To understand the importance of the ancillary modules for BlCel5B activity, enzymatic assays were carried out using four enzyme mutants: a CBM46 deletion (ΔCBM46) and an Ig-like + CBM46 deletion (ΔIg-CBM46) as well as point mutations of the CBM46 inner surface residues W479A and W481A.	RESULTS
+145	153	deletion	experimental_method	To understand the importance of the ancillary modules for BlCel5B activity, enzymatic assays were carried out using four enzyme mutants: a CBM46 deletion (ΔCBM46) and an Ig-like + CBM46 deletion (ΔIg-CBM46) as well as point mutations of the CBM46 inner surface residues W479A and W481A.	RESULTS
+155	161	ΔCBM46	mutant	To understand the importance of the ancillary modules for BlCel5B activity, enzymatic assays were carried out using four enzyme mutants: a CBM46 deletion (ΔCBM46) and an Ig-like + CBM46 deletion (ΔIg-CBM46) as well as point mutations of the CBM46 inner surface residues W479A and W481A.	RESULTS
+170	177	Ig-like	structure_element	To understand the importance of the ancillary modules for BlCel5B activity, enzymatic assays were carried out using four enzyme mutants: a CBM46 deletion (ΔCBM46) and an Ig-like + CBM46 deletion (ΔIg-CBM46) as well as point mutations of the CBM46 inner surface residues W479A and W481A.	RESULTS
+180	185	CBM46	structure_element	To understand the importance of the ancillary modules for BlCel5B activity, enzymatic assays were carried out using four enzyme mutants: a CBM46 deletion (ΔCBM46) and an Ig-like + CBM46 deletion (ΔIg-CBM46) as well as point mutations of the CBM46 inner surface residues W479A and W481A.	RESULTS
+186	194	deletion	experimental_method	To understand the importance of the ancillary modules for BlCel5B activity, enzymatic assays were carried out using four enzyme mutants: a CBM46 deletion (ΔCBM46) and an Ig-like + CBM46 deletion (ΔIg-CBM46) as well as point mutations of the CBM46 inner surface residues W479A and W481A.	RESULTS
+196	205	ΔIg-CBM46	mutant	To understand the importance of the ancillary modules for BlCel5B activity, enzymatic assays were carried out using four enzyme mutants: a CBM46 deletion (ΔCBM46) and an Ig-like + CBM46 deletion (ΔIg-CBM46) as well as point mutations of the CBM46 inner surface residues W479A and W481A.	RESULTS
+218	233	point mutations	experimental_method	To understand the importance of the ancillary modules for BlCel5B activity, enzymatic assays were carried out using four enzyme mutants: a CBM46 deletion (ΔCBM46) and an Ig-like + CBM46 deletion (ΔIg-CBM46) as well as point mutations of the CBM46 inner surface residues W479A and W481A.	RESULTS
+241	246	CBM46	structure_element	To understand the importance of the ancillary modules for BlCel5B activity, enzymatic assays were carried out using four enzyme mutants: a CBM46 deletion (ΔCBM46) and an Ig-like + CBM46 deletion (ΔIg-CBM46) as well as point mutations of the CBM46 inner surface residues W479A and W481A.	RESULTS
+270	275	W479A	mutant	To understand the importance of the ancillary modules for BlCel5B activity, enzymatic assays were carried out using four enzyme mutants: a CBM46 deletion (ΔCBM46) and an Ig-like + CBM46 deletion (ΔIg-CBM46) as well as point mutations of the CBM46 inner surface residues W479A and W481A.	RESULTS
+280	285	W481A	mutant	To understand the importance of the ancillary modules for BlCel5B activity, enzymatic assays were carried out using four enzyme mutants: a CBM46 deletion (ΔCBM46) and an Ig-like + CBM46 deletion (ΔIg-CBM46) as well as point mutations of the CBM46 inner surface residues W479A and W481A.	RESULTS
+6	13	mutants	protein_state	These mutants were expressed and purified as described for the wild-type enzyme.	RESULTS
+19	41	expressed and purified	experimental_method	These mutants were expressed and purified as described for the wild-type enzyme.	RESULTS
+63	72	wild-type	protein_state	These mutants were expressed and purified as described for the wild-type enzyme.	RESULTS
+27	44	deletion variants	protein_state	Strikingly, neither of the deletion variants exhibited detectable activity toward any of the substrates tested using full-length BlCel5B (Table 1), demonstrating that the Ig-like module and the CBM46 are essential for BlCel5B activity.	RESULTS
+117	128	full-length	protein_state	Strikingly, neither of the deletion variants exhibited detectable activity toward any of the substrates tested using full-length BlCel5B (Table 1), demonstrating that the Ig-like module and the CBM46 are essential for BlCel5B activity.	RESULTS
+129	136	BlCel5B	protein	Strikingly, neither of the deletion variants exhibited detectable activity toward any of the substrates tested using full-length BlCel5B (Table 1), demonstrating that the Ig-like module and the CBM46 are essential for BlCel5B activity.	RESULTS
+171	185	Ig-like module	structure_element	Strikingly, neither of the deletion variants exhibited detectable activity toward any of the substrates tested using full-length BlCel5B (Table 1), demonstrating that the Ig-like module and the CBM46 are essential for BlCel5B activity.	RESULTS
+194	199	CBM46	structure_element	Strikingly, neither of the deletion variants exhibited detectable activity toward any of the substrates tested using full-length BlCel5B (Table 1), demonstrating that the Ig-like module and the CBM46 are essential for BlCel5B activity.	RESULTS
+218	225	BlCel5B	protein	Strikingly, neither of the deletion variants exhibited detectable activity toward any of the substrates tested using full-length BlCel5B (Table 1), demonstrating that the Ig-like module and the CBM46 are essential for BlCel5B activity.	RESULTS
+0	20	Thermal shift assays	experimental_method	Thermal shift assays were conducted to confirm structural stability of the mutants (Supplementary Fig. 1).	RESULTS
+75	82	mutants	protein_state	Thermal shift assays were conducted to confirm structural stability of the mutants (Supplementary Fig. 1).	RESULTS
+37	57	melting temperatures	evidence	All of the constructs showed similar melting temperatures: 62 °C for BlCel5B, 58 °C for BlCel5BΔCBM46, 56 °C for BlCel5BΔIg-CBM46, 65 °C for BlCel5BW479A and 59 °C for BlCel5BW479A, thus confirming their proper overall fold.	RESULTS
+69	76	BlCel5B	protein	All of the constructs showed similar melting temperatures: 62 °C for BlCel5B, 58 °C for BlCel5BΔCBM46, 56 °C for BlCel5BΔIg-CBM46, 65 °C for BlCel5BW479A and 59 °C for BlCel5BW479A, thus confirming their proper overall fold.	RESULTS
+88	101	BlCel5BΔCBM46	mutant	All of the constructs showed similar melting temperatures: 62 °C for BlCel5B, 58 °C for BlCel5BΔCBM46, 56 °C for BlCel5BΔIg-CBM46, 65 °C for BlCel5BW479A and 59 °C for BlCel5BW479A, thus confirming their proper overall fold.	RESULTS
+113	129	BlCel5BΔIg-CBM46	mutant	All of the constructs showed similar melting temperatures: 62 °C for BlCel5B, 58 °C for BlCel5BΔCBM46, 56 °C for BlCel5BΔIg-CBM46, 65 °C for BlCel5BW479A and 59 °C for BlCel5BW479A, thus confirming their proper overall fold.	RESULTS
+141	153	BlCel5BW479A	mutant	All of the constructs showed similar melting temperatures: 62 °C for BlCel5B, 58 °C for BlCel5BΔCBM46, 56 °C for BlCel5BΔIg-CBM46, 65 °C for BlCel5BW479A and 59 °C for BlCel5BW479A, thus confirming their proper overall fold.	RESULTS
+168	180	BlCel5BW479A	mutant	All of the constructs showed similar melting temperatures: 62 °C for BlCel5B, 58 °C for BlCel5BΔCBM46, 56 °C for BlCel5BΔIg-CBM46, 65 °C for BlCel5BW479A and 59 °C for BlCel5BW479A, thus confirming their proper overall fold.	RESULTS
+37	42	CBM46	structure_element	We also examined the function of the CBM46 inner surface residues W479 and W481 (Fig. 1A) in BlCel5B activity by performing enzymatic assays with W479A and W481A mutants.	RESULTS
+49	56	surface	site	We also examined the function of the CBM46 inner surface residues W479 and W481 (Fig. 1A) in BlCel5B activity by performing enzymatic assays with W479A and W481A mutants.	RESULTS
+66	70	W479	residue_name_number	We also examined the function of the CBM46 inner surface residues W479 and W481 (Fig. 1A) in BlCel5B activity by performing enzymatic assays with W479A and W481A mutants.	RESULTS
+75	79	W481	residue_name_number	We also examined the function of the CBM46 inner surface residues W479 and W481 (Fig. 1A) in BlCel5B activity by performing enzymatic assays with W479A and W481A mutants.	RESULTS
+93	100	BlCel5B	protein	We also examined the function of the CBM46 inner surface residues W479 and W481 (Fig. 1A) in BlCel5B activity by performing enzymatic assays with W479A and W481A mutants.	RESULTS
+124	140	enzymatic assays	experimental_method	We also examined the function of the CBM46 inner surface residues W479 and W481 (Fig. 1A) in BlCel5B activity by performing enzymatic assays with W479A and W481A mutants.	RESULTS
+146	151	W479A	mutant	We also examined the function of the CBM46 inner surface residues W479 and W481 (Fig. 1A) in BlCel5B activity by performing enzymatic assays with W479A and W481A mutants.	RESULTS
+156	161	W481A	mutant	We also examined the function of the CBM46 inner surface residues W479 and W481 (Fig. 1A) in BlCel5B activity by performing enzymatic assays with W479A and W481A mutants.	RESULTS
+162	169	mutants	protein_state	We also examined the function of the CBM46 inner surface residues W479 and W481 (Fig. 1A) in BlCel5B activity by performing enzymatic assays with W479A and W481A mutants.	RESULTS
+5	14	mutations	experimental_method	Both mutations reduced enzymatic activity toward all tested substrates (Table 1), with W481A having a stronger effect than W479A (~64% vs. 79% activity relative to wt BlCel5B using β-glucan and ~10% vs. 50% using CMC).	RESULTS
+87	92	W481A	mutant	Both mutations reduced enzymatic activity toward all tested substrates (Table 1), with W481A having a stronger effect than W479A (~64% vs. 79% activity relative to wt BlCel5B using β-glucan and ~10% vs. 50% using CMC).	RESULTS
+123	128	W479A	mutant	Both mutations reduced enzymatic activity toward all tested substrates (Table 1), with W481A having a stronger effect than W479A (~64% vs. 79% activity relative to wt BlCel5B using β-glucan and ~10% vs. 50% using CMC).	RESULTS
+164	166	wt	protein_state	Both mutations reduced enzymatic activity toward all tested substrates (Table 1), with W481A having a stronger effect than W479A (~64% vs. 79% activity relative to wt BlCel5B using β-glucan and ~10% vs. 50% using CMC).	RESULTS
+167	174	BlCel5B	protein	Both mutations reduced enzymatic activity toward all tested substrates (Table 1), with W481A having a stronger effect than W479A (~64% vs. 79% activity relative to wt BlCel5B using β-glucan and ~10% vs. 50% using CMC).	RESULTS
+181	189	β-glucan	chemical	Both mutations reduced enzymatic activity toward all tested substrates (Table 1), with W481A having a stronger effect than W479A (~64% vs. 79% activity relative to wt BlCel5B using β-glucan and ~10% vs. 50% using CMC).	RESULTS
+213	216	CMC	chemical	Both mutations reduced enzymatic activity toward all tested substrates (Table 1), with W481A having a stronger effect than W479A (~64% vs. 79% activity relative to wt BlCel5B using β-glucan and ~10% vs. 50% using CMC).	RESULTS
+20	25	CBM46	structure_element	This indicates that CBM46 must interact with the substrate via residues W479 and W481.	RESULTS
+72	76	W479	residue_name_number	This indicates that CBM46 must interact with the substrate via residues W479 and W481.	RESULTS
+81	85	W481	residue_name_number	This indicates that CBM46 must interact with the substrate via residues W479 and W481.	RESULTS
+19	26	BlCel5B	protein	However, since the BlCel5B crystal structure exhibits no close contact between these residues and the substrate, these results suggest the existence of large-amplitude interdomain motions that may enable direct interactions between CBM46 and the carbohydrate.	RESULTS
+27	44	crystal structure	evidence	However, since the BlCel5B crystal structure exhibits no close contact between these residues and the substrate, these results suggest the existence of large-amplitude interdomain motions that may enable direct interactions between CBM46 and the carbohydrate.	RESULTS
+57	62	close	protein_state	However, since the BlCel5B crystal structure exhibits no close contact between these residues and the substrate, these results suggest the existence of large-amplitude interdomain motions that may enable direct interactions between CBM46 and the carbohydrate.	RESULTS
+232	237	CBM46	structure_element	However, since the BlCel5B crystal structure exhibits no close contact between these residues and the substrate, these results suggest the existence of large-amplitude interdomain motions that may enable direct interactions between CBM46 and the carbohydrate.	RESULTS
+246	258	carbohydrate	chemical	However, since the BlCel5B crystal structure exhibits no close contact between these residues and the substrate, these results suggest the existence of large-amplitude interdomain motions that may enable direct interactions between CBM46 and the carbohydrate.	RESULTS
+0	7	BlCelB5	protein	BlCelB5 dynamics and binding-site architecture	RESULTS
+21	33	binding-site	site	BlCelB5 dynamics and binding-site architecture	RESULTS
+0	18	Molecular dynamics	experimental_method	Molecular dynamics (MD) simulations were performed to investigate the conformational mobility of BlCel5B.	RESULTS
+20	22	MD	experimental_method	Molecular dynamics (MD) simulations were performed to investigate the conformational mobility of BlCel5B.	RESULTS
+24	35	simulations	experimental_method	Molecular dynamics (MD) simulations were performed to investigate the conformational mobility of BlCel5B.	RESULTS
+97	104	BlCel5B	protein	Molecular dynamics (MD) simulations were performed to investigate the conformational mobility of BlCel5B.	RESULTS
+7	18	simulations	experimental_method	In the simulations of the crystal structure for BlCel5B bound to C4, the substrate dissociates from the protein within the first 100 ns of the simulation time (Supplementary Fig. 2A).	RESULTS
+26	43	crystal structure	evidence	In the simulations of the crystal structure for BlCel5B bound to C4, the substrate dissociates from the protein within the first 100 ns of the simulation time (Supplementary Fig. 2A).	RESULTS
+48	55	BlCel5B	protein	In the simulations of the crystal structure for BlCel5B bound to C4, the substrate dissociates from the protein within the first 100 ns of the simulation time (Supplementary Fig. 2A).	RESULTS
+56	64	bound to	protein_state	In the simulations of the crystal structure for BlCel5B bound to C4, the substrate dissociates from the protein within the first 100 ns of the simulation time (Supplementary Fig. 2A).	RESULTS
+65	67	C4	chemical	In the simulations of the crystal structure for BlCel5B bound to C4, the substrate dissociates from the protein within the first 100 ns of the simulation time (Supplementary Fig. 2A).	RESULTS
+143	153	simulation	experimental_method	In the simulations of the crystal structure for BlCel5B bound to C4, the substrate dissociates from the protein within the first 100 ns of the simulation time (Supplementary Fig. 2A).	RESULTS
+31	44	cellotetraose	chemical	This observation suggests that cellotetraose does not exhibit detectable affinity for this specific BlCel5B conformation in solution, as one might otherwise expect for a reaction product.	RESULTS
+100	107	BlCel5B	protein	This observation suggests that cellotetraose does not exhibit detectable affinity for this specific BlCel5B conformation in solution, as one might otherwise expect for a reaction product.	RESULTS
+71	78	BlCel5B	protein	No changes beyond local fluctuations were observed in any of the three BlCel5B domains within the time scale of these runs (400 ns; Supplementary Fig. 2B).	RESULTS
+13	18	CBM46	structure_element	However, the CBM46 and Ig-like domains did exhibit rigid body-like motions relative to the CD, with rmsd values around 2.3 Å and 1.8 Å, respectively, suggesting that BlCel5B may execute large-amplitude interdomain motions over longer time scales (Supplementary Fig. 2B,C).	RESULTS
+23	38	Ig-like domains	structure_element	However, the CBM46 and Ig-like domains did exhibit rigid body-like motions relative to the CD, with rmsd values around 2.3 Å and 1.8 Å, respectively, suggesting that BlCel5B may execute large-amplitude interdomain motions over longer time scales (Supplementary Fig. 2B,C).	RESULTS
+91	93	CD	structure_element	However, the CBM46 and Ig-like domains did exhibit rigid body-like motions relative to the CD, with rmsd values around 2.3 Å and 1.8 Å, respectively, suggesting that BlCel5B may execute large-amplitude interdomain motions over longer time scales (Supplementary Fig. 2B,C).	RESULTS
+100	104	rmsd	evidence	However, the CBM46 and Ig-like domains did exhibit rigid body-like motions relative to the CD, with rmsd values around 2.3 Å and 1.8 Å, respectively, suggesting that BlCel5B may execute large-amplitude interdomain motions over longer time scales (Supplementary Fig. 2B,C).	RESULTS
+166	173	BlCel5B	protein	However, the CBM46 and Ig-like domains did exhibit rigid body-like motions relative to the CD, with rmsd values around 2.3 Å and 1.8 Å, respectively, suggesting that BlCel5B may execute large-amplitude interdomain motions over longer time scales (Supplementary Fig. 2B,C).	RESULTS
+13	24	simulations	experimental_method	Accordingly, simulations were then performed using accelerated molecular dynamics (aMD) techniques to probe BlCel5B interdomain motions.	RESULTS
+51	81	accelerated molecular dynamics	experimental_method	Accordingly, simulations were then performed using accelerated molecular dynamics (aMD) techniques to probe BlCel5B interdomain motions.	RESULTS
+83	86	aMD	experimental_method	Accordingly, simulations were then performed using accelerated molecular dynamics (aMD) techniques to probe BlCel5B interdomain motions.	RESULTS
+108	115	BlCel5B	protein	Accordingly, simulations were then performed using accelerated molecular dynamics (aMD) techniques to probe BlCel5B interdomain motions.	RESULTS
+0	3	aMD	experimental_method	aMD enhances conformational sampling by raising the basins of the dihedral potential energy surface without affecting the general form of the atomistic potential, thereby increasing transition rates between different local minima.	RESULTS
+66	99	dihedral potential energy surface	evidence	aMD enhances conformational sampling by raising the basins of the dihedral potential energy surface without affecting the general form of the atomistic potential, thereby increasing transition rates between different local minima.	RESULTS
+0	3	aMD	experimental_method	aMD trajectories corresponding to more than 1.0 μs of conventional MD runs were generated.	RESULTS
+4	16	trajectories	evidence	aMD trajectories corresponding to more than 1.0 μs of conventional MD runs were generated.	RESULTS
+67	69	MD	experimental_method	aMD trajectories corresponding to more than 1.0 μs of conventional MD runs were generated.	RESULTS
+13	24	simulations	experimental_method	During these simulations, we observed occlusive conformations between CBM46 and CD that resulted in a rearrangement of the enzyme’s architecture around the active site (Video S1).	RESULTS
+70	75	CBM46	structure_element	During these simulations, we observed occlusive conformations between CBM46 and CD that resulted in a rearrangement of the enzyme’s architecture around the active site (Video S1).	RESULTS
+80	82	CD	structure_element	During these simulations, we observed occlusive conformations between CBM46 and CD that resulted in a rearrangement of the enzyme’s architecture around the active site (Video S1).	RESULTS
+156	167	active site	site	During these simulations, we observed occlusive conformations between CBM46 and CD that resulted in a rearrangement of the enzyme’s architecture around the active site (Video S1).	RESULTS
+16	23	BlCel5B	protein	Figure 3A shows BlCel5B in the crystallographic conformation (red) and in a selected configuration obtained with aMD (blue) in the absence of the substrate.	RESULTS
+31	47	crystallographic	experimental_method	Figure 3A shows BlCel5B in the crystallographic conformation (red) and in a selected configuration obtained with aMD (blue) in the absence of the substrate.	RESULTS
+113	116	aMD	experimental_method	Figure 3A shows BlCel5B in the crystallographic conformation (red) and in a selected configuration obtained with aMD (blue) in the absence of the substrate.	RESULTS
+131	141	absence of	protein_state	Figure 3A shows BlCel5B in the crystallographic conformation (red) and in a selected configuration obtained with aMD (blue) in the absence of the substrate.	RESULTS
+61	69	distance	evidence	Interdomain motions were gauged by the time evolution of the distance between the α carbons of residues I120 and E477 (represented as spheres in Fig. 3A), belonging to the CD and CBM46, respectively.	RESULTS
+104	108	I120	residue_name_number	Interdomain motions were gauged by the time evolution of the distance between the α carbons of residues I120 and E477 (represented as spheres in Fig. 3A), belonging to the CD and CBM46, respectively.	RESULTS
+113	117	E477	residue_name_number	Interdomain motions were gauged by the time evolution of the distance between the α carbons of residues I120 and E477 (represented as spheres in Fig. 3A), belonging to the CD and CBM46, respectively.	RESULTS
+172	174	CD	structure_element	Interdomain motions were gauged by the time evolution of the distance between the α carbons of residues I120 and E477 (represented as spheres in Fig. 3A), belonging to the CD and CBM46, respectively.	RESULTS
+179	184	CBM46	structure_element	Interdomain motions were gauged by the time evolution of the distance between the α carbons of residues I120 and E477 (represented as spheres in Fig. 3A), belonging to the CD and CBM46, respectively.	RESULTS
+25	29	I120	residue_name_number	Figure 3C shows that the I120-E477 distance (red curve) gradually decreases from ~35 Å to ~7 Å within the first half of the 1.0 μs aMD trajectory, indicating a transition between the semi-open (crystallographic) and occluded (aMD sampled) configurations.	RESULTS
+30	34	E477	residue_name_number	Figure 3C shows that the I120-E477 distance (red curve) gradually decreases from ~35 Å to ~7 Å within the first half of the 1.0 μs aMD trajectory, indicating a transition between the semi-open (crystallographic) and occluded (aMD sampled) configurations.	RESULTS
+35	43	distance	evidence	Figure 3C shows that the I120-E477 distance (red curve) gradually decreases from ~35 Å to ~7 Å within the first half of the 1.0 μs aMD trajectory, indicating a transition between the semi-open (crystallographic) and occluded (aMD sampled) configurations.	RESULTS
+131	134	aMD	experimental_method	Figure 3C shows that the I120-E477 distance (red curve) gradually decreases from ~35 Å to ~7 Å within the first half of the 1.0 μs aMD trajectory, indicating a transition between the semi-open (crystallographic) and occluded (aMD sampled) configurations.	RESULTS
+135	145	trajectory	evidence	Figure 3C shows that the I120-E477 distance (red curve) gradually decreases from ~35 Å to ~7 Å within the first half of the 1.0 μs aMD trajectory, indicating a transition between the semi-open (crystallographic) and occluded (aMD sampled) configurations.	RESULTS
+183	192	semi-open	protein_state	Figure 3C shows that the I120-E477 distance (red curve) gradually decreases from ~35 Å to ~7 Å within the first half of the 1.0 μs aMD trajectory, indicating a transition between the semi-open (crystallographic) and occluded (aMD sampled) configurations.	RESULTS
+194	210	crystallographic	experimental_method	Figure 3C shows that the I120-E477 distance (red curve) gradually decreases from ~35 Å to ~7 Å within the first half of the 1.0 μs aMD trajectory, indicating a transition between the semi-open (crystallographic) and occluded (aMD sampled) configurations.	RESULTS
+216	224	occluded	protein_state	Figure 3C shows that the I120-E477 distance (red curve) gradually decreases from ~35 Å to ~7 Å within the first half of the 1.0 μs aMD trajectory, indicating a transition between the semi-open (crystallographic) and occluded (aMD sampled) configurations.	RESULTS
+226	229	aMD	experimental_method	Figure 3C shows that the I120-E477 distance (red curve) gradually decreases from ~35 Å to ~7 Å within the first half of the 1.0 μs aMD trajectory, indicating a transition between the semi-open (crystallographic) and occluded (aMD sampled) configurations.	RESULTS
+30	44	aMD simulation	experimental_method	During the second half of the aMD simulation, the full-length enzyme remained in the closed conformation, with the CBM46 covering the carbohydrate-binding site.	RESULTS
+50	61	full-length	protein_state	During the second half of the aMD simulation, the full-length enzyme remained in the closed conformation, with the CBM46 covering the carbohydrate-binding site.	RESULTS
+85	91	closed	protein_state	During the second half of the aMD simulation, the full-length enzyme remained in the closed conformation, with the CBM46 covering the carbohydrate-binding site.	RESULTS
+115	120	CBM46	structure_element	During the second half of the aMD simulation, the full-length enzyme remained in the closed conformation, with the CBM46 covering the carbohydrate-binding site.	RESULTS
+134	159	carbohydrate-binding site	site	During the second half of the aMD simulation, the full-length enzyme remained in the closed conformation, with the CBM46 covering the carbohydrate-binding site.	RESULTS
+27	34	BlCel5B	protein	These results suggest that BlCel5B undergoes large-scale interdomain movements that enable interactions between CBM46 and the substrate bound to the CD.	RESULTS
+112	117	CBM46	structure_element	These results suggest that BlCel5B undergoes large-scale interdomain movements that enable interactions between CBM46 and the substrate bound to the CD.	RESULTS
+136	144	bound to	protein_state	These results suggest that BlCel5B undergoes large-scale interdomain movements that enable interactions between CBM46 and the substrate bound to the CD.	RESULTS
+149	151	CD	structure_element	These results suggest that BlCel5B undergoes large-scale interdomain movements that enable interactions between CBM46 and the substrate bound to the CD.	RESULTS
+29	36	BlCel5B	protein	To study the interactions of BlCel5B with a non-hydrolyzed glucan chain, we built a model structure with a cellooctaose (C8) chain spanning the entire positive (+1 to +4) and negative (−4 to −1) subsites of the enzyme.	RESULTS
+59	65	glucan	chemical	To study the interactions of BlCel5B with a non-hydrolyzed glucan chain, we built a model structure with a cellooctaose (C8) chain spanning the entire positive (+1 to +4) and negative (−4 to −1) subsites of the enzyme.	RESULTS
+90	99	structure	evidence	To study the interactions of BlCel5B with a non-hydrolyzed glucan chain, we built a model structure with a cellooctaose (C8) chain spanning the entire positive (+1 to +4) and negative (−4 to −1) subsites of the enzyme.	RESULTS
+107	119	cellooctaose	chemical	To study the interactions of BlCel5B with a non-hydrolyzed glucan chain, we built a model structure with a cellooctaose (C8) chain spanning the entire positive (+1 to +4) and negative (−4 to −1) subsites of the enzyme.	RESULTS
+121	123	C8	chemical	To study the interactions of BlCel5B with a non-hydrolyzed glucan chain, we built a model structure with a cellooctaose (C8) chain spanning the entire positive (+1 to +4) and negative (−4 to −1) subsites of the enzyme.	RESULTS
+151	170	positive (+1 to +4)	site	To study the interactions of BlCel5B with a non-hydrolyzed glucan chain, we built a model structure with a cellooctaose (C8) chain spanning the entire positive (+1 to +4) and negative (−4 to −1) subsites of the enzyme.	RESULTS
+175	194	negative (−4 to −1)	site	To study the interactions of BlCel5B with a non-hydrolyzed glucan chain, we built a model structure with a cellooctaose (C8) chain spanning the entire positive (+1 to +4) and negative (−4 to −1) subsites of the enzyme.	RESULTS
+195	203	subsites	site	To study the interactions of BlCel5B with a non-hydrolyzed glucan chain, we built a model structure with a cellooctaose (C8) chain spanning the entire positive (+1 to +4) and negative (−4 to −1) subsites of the enzyme.	RESULTS
+35	42	BlCel5B	protein	Starting from the crystallographic BlCel5B conformation, the C8 molecule deviated significantly from the active site and assumed a non-productive binding mode (Supplementary Fig. 2D).	RESULTS
+61	63	C8	chemical	Starting from the crystallographic BlCel5B conformation, the C8 molecule deviated significantly from the active site and assumed a non-productive binding mode (Supplementary Fig. 2D).	RESULTS
+105	116	active site	site	Starting from the crystallographic BlCel5B conformation, the C8 molecule deviated significantly from the active site and assumed a non-productive binding mode (Supplementary Fig. 2D).	RESULTS
+35	39	open	protein_state	This observation suggests that the open conformation of BlCel5B is not able to hold the substrate in a position suitable for hydrolysis (Supplementary Fig. 2E).	RESULTS
+56	63	BlCel5B	protein	This observation suggests that the open conformation of BlCel5B is not able to hold the substrate in a position suitable for hydrolysis (Supplementary Fig. 2E).	RESULTS
+30	40	BlCel5B-C8	complex_assembly	However, after subjecting the BlCel5B-C8 complex to a 0.5 μs aMD simulation with harmonic restraints on the C8 chain to prevent it from deviating from the productive binding mode, the CBM46 readily closed over the CD and trapped the C8 chain in position for hydrolysis (Fig. 3B).	RESULTS
+61	75	aMD simulation	experimental_method	However, after subjecting the BlCel5B-C8 complex to a 0.5 μs aMD simulation with harmonic restraints on the C8 chain to prevent it from deviating from the productive binding mode, the CBM46 readily closed over the CD and trapped the C8 chain in position for hydrolysis (Fig. 3B).	RESULTS
+108	110	C8	chemical	However, after subjecting the BlCel5B-C8 complex to a 0.5 μs aMD simulation with harmonic restraints on the C8 chain to prevent it from deviating from the productive binding mode, the CBM46 readily closed over the CD and trapped the C8 chain in position for hydrolysis (Fig. 3B).	RESULTS
+184	189	CBM46	structure_element	However, after subjecting the BlCel5B-C8 complex to a 0.5 μs aMD simulation with harmonic restraints on the C8 chain to prevent it from deviating from the productive binding mode, the CBM46 readily closed over the CD and trapped the C8 chain in position for hydrolysis (Fig. 3B).	RESULTS
+198	204	closed	protein_state	However, after subjecting the BlCel5B-C8 complex to a 0.5 μs aMD simulation with harmonic restraints on the C8 chain to prevent it from deviating from the productive binding mode, the CBM46 readily closed over the CD and trapped the C8 chain in position for hydrolysis (Fig. 3B).	RESULTS
+214	216	CD	structure_element	However, after subjecting the BlCel5B-C8 complex to a 0.5 μs aMD simulation with harmonic restraints on the C8 chain to prevent it from deviating from the productive binding mode, the CBM46 readily closed over the CD and trapped the C8 chain in position for hydrolysis (Fig. 3B).	RESULTS
+233	235	C8	chemical	However, after subjecting the BlCel5B-C8 complex to a 0.5 μs aMD simulation with harmonic restraints on the C8 chain to prevent it from deviating from the productive binding mode, the CBM46 readily closed over the CD and trapped the C8 chain in position for hydrolysis (Fig. 3B).	RESULTS
+7	18	presence of	protein_state	In the presence of the substrate, CBM46 adopts a final conformation intermediate between the crystallographic structure and that observed in the substrate-free BlCel5B aMD simulations; this is illustrated by the I120-E477 distance, which stabilizes near 20 Å in the closed configuration that traps the C8 molecule (in contrast to ~7 Å for substrate-free BlCel5B) (Fig. 3C).	RESULTS
+34	39	CBM46	structure_element	In the presence of the substrate, CBM46 adopts a final conformation intermediate between the crystallographic structure and that observed in the substrate-free BlCel5B aMD simulations; this is illustrated by the I120-E477 distance, which stabilizes near 20 Å in the closed configuration that traps the C8 molecule (in contrast to ~7 Å for substrate-free BlCel5B) (Fig. 3C).	RESULTS
+93	119	crystallographic structure	evidence	In the presence of the substrate, CBM46 adopts a final conformation intermediate between the crystallographic structure and that observed in the substrate-free BlCel5B aMD simulations; this is illustrated by the I120-E477 distance, which stabilizes near 20 Å in the closed configuration that traps the C8 molecule (in contrast to ~7 Å for substrate-free BlCel5B) (Fig. 3C).	RESULTS
+145	159	substrate-free	protein_state	In the presence of the substrate, CBM46 adopts a final conformation intermediate between the crystallographic structure and that observed in the substrate-free BlCel5B aMD simulations; this is illustrated by the I120-E477 distance, which stabilizes near 20 Å in the closed configuration that traps the C8 molecule (in contrast to ~7 Å for substrate-free BlCel5B) (Fig. 3C).	RESULTS
+160	167	BlCel5B	protein	In the presence of the substrate, CBM46 adopts a final conformation intermediate between the crystallographic structure and that observed in the substrate-free BlCel5B aMD simulations; this is illustrated by the I120-E477 distance, which stabilizes near 20 Å in the closed configuration that traps the C8 molecule (in contrast to ~7 Å for substrate-free BlCel5B) (Fig. 3C).	RESULTS
+168	183	aMD simulations	experimental_method	In the presence of the substrate, CBM46 adopts a final conformation intermediate between the crystallographic structure and that observed in the substrate-free BlCel5B aMD simulations; this is illustrated by the I120-E477 distance, which stabilizes near 20 Å in the closed configuration that traps the C8 molecule (in contrast to ~7 Å for substrate-free BlCel5B) (Fig. 3C).	RESULTS
+212	216	I120	residue_name_number	In the presence of the substrate, CBM46 adopts a final conformation intermediate between the crystallographic structure and that observed in the substrate-free BlCel5B aMD simulations; this is illustrated by the I120-E477 distance, which stabilizes near 20 Å in the closed configuration that traps the C8 molecule (in contrast to ~7 Å for substrate-free BlCel5B) (Fig. 3C).	RESULTS
+217	221	E477	residue_name_number	In the presence of the substrate, CBM46 adopts a final conformation intermediate between the crystallographic structure and that observed in the substrate-free BlCel5B aMD simulations; this is illustrated by the I120-E477 distance, which stabilizes near 20 Å in the closed configuration that traps the C8 molecule (in contrast to ~7 Å for substrate-free BlCel5B) (Fig. 3C).	RESULTS
+222	230	distance	evidence	In the presence of the substrate, CBM46 adopts a final conformation intermediate between the crystallographic structure and that observed in the substrate-free BlCel5B aMD simulations; this is illustrated by the I120-E477 distance, which stabilizes near 20 Å in the closed configuration that traps the C8 molecule (in contrast to ~7 Å for substrate-free BlCel5B) (Fig. 3C).	RESULTS
+266	272	closed	protein_state	In the presence of the substrate, CBM46 adopts a final conformation intermediate between the crystallographic structure and that observed in the substrate-free BlCel5B aMD simulations; this is illustrated by the I120-E477 distance, which stabilizes near 20 Å in the closed configuration that traps the C8 molecule (in contrast to ~7 Å for substrate-free BlCel5B) (Fig. 3C).	RESULTS
+302	304	C8	chemical	In the presence of the substrate, CBM46 adopts a final conformation intermediate between the crystallographic structure and that observed in the substrate-free BlCel5B aMD simulations; this is illustrated by the I120-E477 distance, which stabilizes near 20 Å in the closed configuration that traps the C8 molecule (in contrast to ~7 Å for substrate-free BlCel5B) (Fig. 3C).	RESULTS
+339	353	substrate-free	protein_state	In the presence of the substrate, CBM46 adopts a final conformation intermediate between the crystallographic structure and that observed in the substrate-free BlCel5B aMD simulations; this is illustrated by the I120-E477 distance, which stabilizes near 20 Å in the closed configuration that traps the C8 molecule (in contrast to ~7 Å for substrate-free BlCel5B) (Fig. 3C).	RESULTS
+354	361	BlCel5B	protein	In the presence of the substrate, CBM46 adopts a final conformation intermediate between the crystallographic structure and that observed in the substrate-free BlCel5B aMD simulations; this is illustrated by the I120-E477 distance, which stabilizes near 20 Å in the closed configuration that traps the C8 molecule (in contrast to ~7 Å for substrate-free BlCel5B) (Fig. 3C).	RESULTS
+5	15	BlCel5B-C8	complex_assembly	This BlCel5B-C8 configuration remains stable over an additional 500 ns of conventional MD simulation with no restraints (Fig. 3C cyan line, Supplementary Fig. 2E,F).	RESULTS
+87	100	MD simulation	experimental_method	This BlCel5B-C8 configuration remains stable over an additional 500 ns of conventional MD simulation with no restraints (Fig. 3C cyan line, Supplementary Fig. 2E,F).	RESULTS
+81	92	simulations	experimental_method	A closer inspection of the productive binding mode obtained from these extensive simulations reveals that the CBM46 tryptophan residues W479 and W481 (along with CD tryptophan residues) play important roles in carbohydrate recognition and orientation by creating a tunnel-like topology along the BlCel5B binding cleft, as depicted in Fig. 3D.	RESULTS
+110	115	CBM46	structure_element	A closer inspection of the productive binding mode obtained from these extensive simulations reveals that the CBM46 tryptophan residues W479 and W481 (along with CD tryptophan residues) play important roles in carbohydrate recognition and orientation by creating a tunnel-like topology along the BlCel5B binding cleft, as depicted in Fig. 3D.	RESULTS
+116	126	tryptophan	residue_name	A closer inspection of the productive binding mode obtained from these extensive simulations reveals that the CBM46 tryptophan residues W479 and W481 (along with CD tryptophan residues) play important roles in carbohydrate recognition and orientation by creating a tunnel-like topology along the BlCel5B binding cleft, as depicted in Fig. 3D.	RESULTS
+136	140	W479	residue_name_number	A closer inspection of the productive binding mode obtained from these extensive simulations reveals that the CBM46 tryptophan residues W479 and W481 (along with CD tryptophan residues) play important roles in carbohydrate recognition and orientation by creating a tunnel-like topology along the BlCel5B binding cleft, as depicted in Fig. 3D.	RESULTS
+145	149	W481	residue_name_number	A closer inspection of the productive binding mode obtained from these extensive simulations reveals that the CBM46 tryptophan residues W479 and W481 (along with CD tryptophan residues) play important roles in carbohydrate recognition and orientation by creating a tunnel-like topology along the BlCel5B binding cleft, as depicted in Fig. 3D.	RESULTS
+162	164	CD	structure_element	A closer inspection of the productive binding mode obtained from these extensive simulations reveals that the CBM46 tryptophan residues W479 and W481 (along with CD tryptophan residues) play important roles in carbohydrate recognition and orientation by creating a tunnel-like topology along the BlCel5B binding cleft, as depicted in Fig. 3D.	RESULTS
+165	175	tryptophan	residue_name	A closer inspection of the productive binding mode obtained from these extensive simulations reveals that the CBM46 tryptophan residues W479 and W481 (along with CD tryptophan residues) play important roles in carbohydrate recognition and orientation by creating a tunnel-like topology along the BlCel5B binding cleft, as depicted in Fig. 3D.	RESULTS
+210	222	carbohydrate	chemical	A closer inspection of the productive binding mode obtained from these extensive simulations reveals that the CBM46 tryptophan residues W479 and W481 (along with CD tryptophan residues) play important roles in carbohydrate recognition and orientation by creating a tunnel-like topology along the BlCel5B binding cleft, as depicted in Fig. 3D.	RESULTS
+265	271	tunnel	site	A closer inspection of the productive binding mode obtained from these extensive simulations reveals that the CBM46 tryptophan residues W479 and W481 (along with CD tryptophan residues) play important roles in carbohydrate recognition and orientation by creating a tunnel-like topology along the BlCel5B binding cleft, as depicted in Fig. 3D.	RESULTS
+296	303	BlCel5B	protein	A closer inspection of the productive binding mode obtained from these extensive simulations reveals that the CBM46 tryptophan residues W479 and W481 (along with CD tryptophan residues) play important roles in carbohydrate recognition and orientation by creating a tunnel-like topology along the BlCel5B binding cleft, as depicted in Fig. 3D.	RESULTS
+304	317	binding cleft	site	A closer inspection of the productive binding mode obtained from these extensive simulations reveals that the CBM46 tryptophan residues W479 and W481 (along with CD tryptophan residues) play important roles in carbohydrate recognition and orientation by creating a tunnel-like topology along the BlCel5B binding cleft, as depicted in Fig. 3D.	RESULTS
+38	43	CBM46	structure_element	Together, these results indicate that CBM46 is a key component of the catalytic active complex, providing an explanation as to why CBM46 is essential for the enzymatic activity of BlCel5B.	RESULTS
+70	86	catalytic active	protein_state	Together, these results indicate that CBM46 is a key component of the catalytic active complex, providing an explanation as to why CBM46 is essential for the enzymatic activity of BlCel5B.	RESULTS
+131	136	CBM46	structure_element	Together, these results indicate that CBM46 is a key component of the catalytic active complex, providing an explanation as to why CBM46 is essential for the enzymatic activity of BlCel5B.	RESULTS
+180	187	BlCel5B	protein	Together, these results indicate that CBM46 is a key component of the catalytic active complex, providing an explanation as to why CBM46 is essential for the enzymatic activity of BlCel5B.	RESULTS
+55	76	atomistic simulations	experimental_method	To enable substantially longer time scales compared to atomistic simulations, we further explored the dynamics of BlCel5B using coarse-grained MD (CG-MD) simulations.	RESULTS
+114	121	BlCel5B	protein	To enable substantially longer time scales compared to atomistic simulations, we further explored the dynamics of BlCel5B using coarse-grained MD (CG-MD) simulations.	RESULTS
+128	145	coarse-grained MD	experimental_method	To enable substantially longer time scales compared to atomistic simulations, we further explored the dynamics of BlCel5B using coarse-grained MD (CG-MD) simulations.	RESULTS
+147	152	CG-MD	experimental_method	To enable substantially longer time scales compared to atomistic simulations, we further explored the dynamics of BlCel5B using coarse-grained MD (CG-MD) simulations.	RESULTS
+154	165	simulations	experimental_method	To enable substantially longer time scales compared to atomistic simulations, we further explored the dynamics of BlCel5B using coarse-grained MD (CG-MD) simulations.	RESULTS
+39	56	CG-MD simulations	experimental_method	We performed three independent ~120 μs CG-MD simulations, for a total of approximately 360 μs of sampling.	RESULTS
+4	12	distance	evidence	The distance between the α carbons of two residues centrally positioned in the CD and CBM46 (Fig. 4A) was monitored, and the results shown in Fig. 4B indicate that the wide-amplitude events described above frequently appear in this time scale.	RESULTS
+79	81	CD	structure_element	The distance between the α carbons of two residues centrally positioned in the CD and CBM46 (Fig. 4A) was monitored, and the results shown in Fig. 4B indicate that the wide-amplitude events described above frequently appear in this time scale.	RESULTS
+86	91	CBM46	structure_element	The distance between the α carbons of two residues centrally positioned in the CD and CBM46 (Fig. 4A) was monitored, and the results shown in Fig. 4B indicate that the wide-amplitude events described above frequently appear in this time scale.	RESULTS
+4	34	computed distance distribution	evidence	The computed distance distribution depicted in Fig. 4C indicates three main conformational states ranging from (I) closed conformations similar to those encountered in the substrate-free aMD simulations, in which CBM46 interacts with the CD to shape the substrate binding site, to (II) semi-open conformations similar to the crystallographic structure, and (III) extended BlCel5B conformations in which the CD and CBM46 are even further apart than in the crystal structure.	RESULTS
+115	121	closed	protein_state	The computed distance distribution depicted in Fig. 4C indicates three main conformational states ranging from (I) closed conformations similar to those encountered in the substrate-free aMD simulations, in which CBM46 interacts with the CD to shape the substrate binding site, to (II) semi-open conformations similar to the crystallographic structure, and (III) extended BlCel5B conformations in which the CD and CBM46 are even further apart than in the crystal structure.	RESULTS
+172	186	substrate-free	protein_state	The computed distance distribution depicted in Fig. 4C indicates three main conformational states ranging from (I) closed conformations similar to those encountered in the substrate-free aMD simulations, in which CBM46 interacts with the CD to shape the substrate binding site, to (II) semi-open conformations similar to the crystallographic structure, and (III) extended BlCel5B conformations in which the CD and CBM46 are even further apart than in the crystal structure.	RESULTS
+187	202	aMD simulations	experimental_method	The computed distance distribution depicted in Fig. 4C indicates three main conformational states ranging from (I) closed conformations similar to those encountered in the substrate-free aMD simulations, in which CBM46 interacts with the CD to shape the substrate binding site, to (II) semi-open conformations similar to the crystallographic structure, and (III) extended BlCel5B conformations in which the CD and CBM46 are even further apart than in the crystal structure.	RESULTS
+213	218	CBM46	structure_element	The computed distance distribution depicted in Fig. 4C indicates three main conformational states ranging from (I) closed conformations similar to those encountered in the substrate-free aMD simulations, in which CBM46 interacts with the CD to shape the substrate binding site, to (II) semi-open conformations similar to the crystallographic structure, and (III) extended BlCel5B conformations in which the CD and CBM46 are even further apart than in the crystal structure.	RESULTS
+238	240	CD	structure_element	The computed distance distribution depicted in Fig. 4C indicates three main conformational states ranging from (I) closed conformations similar to those encountered in the substrate-free aMD simulations, in which CBM46 interacts with the CD to shape the substrate binding site, to (II) semi-open conformations similar to the crystallographic structure, and (III) extended BlCel5B conformations in which the CD and CBM46 are even further apart than in the crystal structure.	RESULTS
+254	276	substrate binding site	site	The computed distance distribution depicted in Fig. 4C indicates three main conformational states ranging from (I) closed conformations similar to those encountered in the substrate-free aMD simulations, in which CBM46 interacts with the CD to shape the substrate binding site, to (II) semi-open conformations similar to the crystallographic structure, and (III) extended BlCel5B conformations in which the CD and CBM46 are even further apart than in the crystal structure.	RESULTS
+286	295	semi-open	protein_state	The computed distance distribution depicted in Fig. 4C indicates three main conformational states ranging from (I) closed conformations similar to those encountered in the substrate-free aMD simulations, in which CBM46 interacts with the CD to shape the substrate binding site, to (II) semi-open conformations similar to the crystallographic structure, and (III) extended BlCel5B conformations in which the CD and CBM46 are even further apart than in the crystal structure.	RESULTS
+325	351	crystallographic structure	evidence	The computed distance distribution depicted in Fig. 4C indicates three main conformational states ranging from (I) closed conformations similar to those encountered in the substrate-free aMD simulations, in which CBM46 interacts with the CD to shape the substrate binding site, to (II) semi-open conformations similar to the crystallographic structure, and (III) extended BlCel5B conformations in which the CD and CBM46 are even further apart than in the crystal structure.	RESULTS
+363	371	extended	protein_state	The computed distance distribution depicted in Fig. 4C indicates three main conformational states ranging from (I) closed conformations similar to those encountered in the substrate-free aMD simulations, in which CBM46 interacts with the CD to shape the substrate binding site, to (II) semi-open conformations similar to the crystallographic structure, and (III) extended BlCel5B conformations in which the CD and CBM46 are even further apart than in the crystal structure.	RESULTS
+372	379	BlCel5B	protein	The computed distance distribution depicted in Fig. 4C indicates three main conformational states ranging from (I) closed conformations similar to those encountered in the substrate-free aMD simulations, in which CBM46 interacts with the CD to shape the substrate binding site, to (II) semi-open conformations similar to the crystallographic structure, and (III) extended BlCel5B conformations in which the CD and CBM46 are even further apart than in the crystal structure.	RESULTS
+407	409	CD	structure_element	The computed distance distribution depicted in Fig. 4C indicates three main conformational states ranging from (I) closed conformations similar to those encountered in the substrate-free aMD simulations, in which CBM46 interacts with the CD to shape the substrate binding site, to (II) semi-open conformations similar to the crystallographic structure, and (III) extended BlCel5B conformations in which the CD and CBM46 are even further apart than in the crystal structure.	RESULTS
+414	419	CBM46	structure_element	The computed distance distribution depicted in Fig. 4C indicates three main conformational states ranging from (I) closed conformations similar to those encountered in the substrate-free aMD simulations, in which CBM46 interacts with the CD to shape the substrate binding site, to (II) semi-open conformations similar to the crystallographic structure, and (III) extended BlCel5B conformations in which the CD and CBM46 are even further apart than in the crystal structure.	RESULTS
+455	472	crystal structure	evidence	The computed distance distribution depicted in Fig. 4C indicates three main conformational states ranging from (I) closed conformations similar to those encountered in the substrate-free aMD simulations, in which CBM46 interacts with the CD to shape the substrate binding site, to (II) semi-open conformations similar to the crystallographic structure, and (III) extended BlCel5B conformations in which the CD and CBM46 are even further apart than in the crystal structure.	RESULTS
+0	7	BlCel5B	protein	BlCel5B conformers fit the SAXS envelope	RESULTS
+27	31	SAXS	experimental_method	BlCel5B conformers fit the SAXS envelope	RESULTS
+32	40	envelope	evidence	BlCel5B conformers fit the SAXS envelope	RESULTS
+0	4	SAXS	experimental_method	SAXS experiments were conducted to assess BlCel5B conformational states in solution, and the results revealed the enzyme in its monomeric form, with average values of Rg = 27.17 Å and Dmax = 87.59 Å (Supplementary Table 2).	RESULTS
+42	49	BlCel5B	protein	SAXS experiments were conducted to assess BlCel5B conformational states in solution, and the results revealed the enzyme in its monomeric form, with average values of Rg = 27.17 Å and Dmax = 87.59 Å (Supplementary Table 2).	RESULTS
+128	137	monomeric	oligomeric_state	SAXS experiments were conducted to assess BlCel5B conformational states in solution, and the results revealed the enzyme in its monomeric form, with average values of Rg = 27.17 Å and Dmax = 87.59 Å (Supplementary Table 2).	RESULTS
+167	169	Rg	evidence	SAXS experiments were conducted to assess BlCel5B conformational states in solution, and the results revealed the enzyme in its monomeric form, with average values of Rg = 27.17 Å and Dmax = 87.59 Å (Supplementary Table 2).	RESULTS
+184	188	Dmax	evidence	SAXS experiments were conducted to assess BlCel5B conformational states in solution, and the results revealed the enzyme in its monomeric form, with average values of Rg = 27.17 Å and Dmax = 87.59 Å (Supplementary Table 2).	RESULTS
+4	30	ab initio dummy atom model	experimental_method	The ab initio dummy atom model (DAM) demonstrated that the SAXS-derived BlCel5B molecular envelope could not be single-handedly filled by any of the main conformational states encountered in the simulations (Fig. 4D).	RESULTS
+32	35	DAM	experimental_method	The ab initio dummy atom model (DAM) demonstrated that the SAXS-derived BlCel5B molecular envelope could not be single-handedly filled by any of the main conformational states encountered in the simulations (Fig. 4D).	RESULTS
+59	63	SAXS	experimental_method	The ab initio dummy atom model (DAM) demonstrated that the SAXS-derived BlCel5B molecular envelope could not be single-handedly filled by any of the main conformational states encountered in the simulations (Fig. 4D).	RESULTS
+72	79	BlCel5B	protein	The ab initio dummy atom model (DAM) demonstrated that the SAXS-derived BlCel5B molecular envelope could not be single-handedly filled by any of the main conformational states encountered in the simulations (Fig. 4D).	RESULTS
+90	98	envelope	evidence	The ab initio dummy atom model (DAM) demonstrated that the SAXS-derived BlCel5B molecular envelope could not be single-handedly filled by any of the main conformational states encountered in the simulations (Fig. 4D).	RESULTS
+195	206	simulations	experimental_method	The ab initio dummy atom model (DAM) demonstrated that the SAXS-derived BlCel5B molecular envelope could not be single-handedly filled by any of the main conformational states encountered in the simulations (Fig. 4D).	RESULTS
+19	30	Kratky plot	evidence	It is known that a Kratky plot exhibits a peak with an elevated baseline at high q for a monodisperse system composed of multi-domain particles with flexible extensions.	RESULTS
+85	92	BlCel5B	protein	Indeed, an elevation of the baseline toward a hyperbolic-like curve was observed for BlCel5B, indicating a considerable degree of molecular mobility in solution (Supplementary Fig. 3).	RESULTS
+151	182	crystallographic and MD studies	experimental_method	Thus, the conformational heterogeneity of the enzyme can be decomposed in structural terms as a combination of conformational states identified in our crystallographic and MD studies.	RESULTS
+18	22	SAXS	experimental_method	We found that the SAXS envelope can be well represented by considering the superimposition of three different representative molecular conformations of BlCel5B (Fig. 4E): a closed or CBM46/CD-occluded conformation extracted from the simulations with a relative weight of 26%, a semi-open conformation represented by the crystal structure corresponding to 40%, and an extended conformation based on simulations that is responsible for 34% of the SAXS envelope.	RESULTS
+23	31	envelope	evidence	We found that the SAXS envelope can be well represented by considering the superimposition of three different representative molecular conformations of BlCel5B (Fig. 4E): a closed or CBM46/CD-occluded conformation extracted from the simulations with a relative weight of 26%, a semi-open conformation represented by the crystal structure corresponding to 40%, and an extended conformation based on simulations that is responsible for 34% of the SAXS envelope.	RESULTS
+75	90	superimposition	experimental_method	We found that the SAXS envelope can be well represented by considering the superimposition of three different representative molecular conformations of BlCel5B (Fig. 4E): a closed or CBM46/CD-occluded conformation extracted from the simulations with a relative weight of 26%, a semi-open conformation represented by the crystal structure corresponding to 40%, and an extended conformation based on simulations that is responsible for 34% of the SAXS envelope.	RESULTS
+152	159	BlCel5B	protein	We found that the SAXS envelope can be well represented by considering the superimposition of three different representative molecular conformations of BlCel5B (Fig. 4E): a closed or CBM46/CD-occluded conformation extracted from the simulations with a relative weight of 26%, a semi-open conformation represented by the crystal structure corresponding to 40%, and an extended conformation based on simulations that is responsible for 34% of the SAXS envelope.	RESULTS
+173	179	closed	protein_state	We found that the SAXS envelope can be well represented by considering the superimposition of three different representative molecular conformations of BlCel5B (Fig. 4E): a closed or CBM46/CD-occluded conformation extracted from the simulations with a relative weight of 26%, a semi-open conformation represented by the crystal structure corresponding to 40%, and an extended conformation based on simulations that is responsible for 34% of the SAXS envelope.	RESULTS
+183	188	CBM46	structure_element	We found that the SAXS envelope can be well represented by considering the superimposition of three different representative molecular conformations of BlCel5B (Fig. 4E): a closed or CBM46/CD-occluded conformation extracted from the simulations with a relative weight of 26%, a semi-open conformation represented by the crystal structure corresponding to 40%, and an extended conformation based on simulations that is responsible for 34% of the SAXS envelope.	RESULTS
+189	191	CD	structure_element	We found that the SAXS envelope can be well represented by considering the superimposition of three different representative molecular conformations of BlCel5B (Fig. 4E): a closed or CBM46/CD-occluded conformation extracted from the simulations with a relative weight of 26%, a semi-open conformation represented by the crystal structure corresponding to 40%, and an extended conformation based on simulations that is responsible for 34% of the SAXS envelope.	RESULTS
+192	200	occluded	protein_state	We found that the SAXS envelope can be well represented by considering the superimposition of three different representative molecular conformations of BlCel5B (Fig. 4E): a closed or CBM46/CD-occluded conformation extracted from the simulations with a relative weight of 26%, a semi-open conformation represented by the crystal structure corresponding to 40%, and an extended conformation based on simulations that is responsible for 34% of the SAXS envelope.	RESULTS
+233	244	simulations	experimental_method	We found that the SAXS envelope can be well represented by considering the superimposition of three different representative molecular conformations of BlCel5B (Fig. 4E): a closed or CBM46/CD-occluded conformation extracted from the simulations with a relative weight of 26%, a semi-open conformation represented by the crystal structure corresponding to 40%, and an extended conformation based on simulations that is responsible for 34% of the SAXS envelope.	RESULTS
+278	287	semi-open	protein_state	We found that the SAXS envelope can be well represented by considering the superimposition of three different representative molecular conformations of BlCel5B (Fig. 4E): a closed or CBM46/CD-occluded conformation extracted from the simulations with a relative weight of 26%, a semi-open conformation represented by the crystal structure corresponding to 40%, and an extended conformation based on simulations that is responsible for 34% of the SAXS envelope.	RESULTS
+320	337	crystal structure	evidence	We found that the SAXS envelope can be well represented by considering the superimposition of three different representative molecular conformations of BlCel5B (Fig. 4E): a closed or CBM46/CD-occluded conformation extracted from the simulations with a relative weight of 26%, a semi-open conformation represented by the crystal structure corresponding to 40%, and an extended conformation based on simulations that is responsible for 34% of the SAXS envelope.	RESULTS
+367	375	extended	protein_state	We found that the SAXS envelope can be well represented by considering the superimposition of three different representative molecular conformations of BlCel5B (Fig. 4E): a closed or CBM46/CD-occluded conformation extracted from the simulations with a relative weight of 26%, a semi-open conformation represented by the crystal structure corresponding to 40%, and an extended conformation based on simulations that is responsible for 34% of the SAXS envelope.	RESULTS
+398	409	simulations	experimental_method	We found that the SAXS envelope can be well represented by considering the superimposition of three different representative molecular conformations of BlCel5B (Fig. 4E): a closed or CBM46/CD-occluded conformation extracted from the simulations with a relative weight of 26%, a semi-open conformation represented by the crystal structure corresponding to 40%, and an extended conformation based on simulations that is responsible for 34% of the SAXS envelope.	RESULTS
+445	449	SAXS	experimental_method	We found that the SAXS envelope can be well represented by considering the superimposition of three different representative molecular conformations of BlCel5B (Fig. 4E): a closed or CBM46/CD-occluded conformation extracted from the simulations with a relative weight of 26%, a semi-open conformation represented by the crystal structure corresponding to 40%, and an extended conformation based on simulations that is responsible for 34% of the SAXS envelope.	RESULTS
+450	458	envelope	evidence	We found that the SAXS envelope can be well represented by considering the superimposition of three different representative molecular conformations of BlCel5B (Fig. 4E): a closed or CBM46/CD-occluded conformation extracted from the simulations with a relative weight of 26%, a semi-open conformation represented by the crystal structure corresponding to 40%, and an extended conformation based on simulations that is responsible for 34% of the SAXS envelope.	RESULTS
+14	38	average scattering curve	evidence	The resulting average scattering curve from this model fits the experimental protein scattering intensity, with χ = 1.89 (Supplementary Fig. 3).	RESULTS
+85	105	scattering intensity	evidence	The resulting average scattering curve from this model fits the experimental protein scattering intensity, with χ = 1.89 (Supplementary Fig. 3).	RESULTS
+112	113	χ	evidence	The resulting average scattering curve from this model fits the experimental protein scattering intensity, with χ = 1.89 (Supplementary Fig. 3).	RESULTS
+0	5	GH5_4	protein_type	GH5_4 phylogenetic analysis	RESULTS
+6	27	phylogenetic analysis	experimental_method	GH5_4 phylogenetic analysis	RESULTS
+150	161	277 and 400	residue_range	After the exclusion of partial sequences and the suppression of highly identical members (higher than 90% identity), 144 sequences containing between 277 and 400 residues were aligned and used to construct a phylogenetic tree (Supplementary Fig. 4A).	RESULTS
+176	183	aligned	experimental_method	After the exclusion of partial sequences and the suppression of highly identical members (higher than 90% identity), 144 sequences containing between 277 and 400 residues were aligned and used to construct a phylogenetic tree (Supplementary Fig. 4A).	RESULTS
+208	225	phylogenetic tree	evidence	After the exclusion of partial sequences and the suppression of highly identical members (higher than 90% identity), 144 sequences containing between 277 and 400 residues were aligned and used to construct a phylogenetic tree (Supplementary Fig. 4A).	RESULTS
+64	67	GH5	protein_type	According to PFAM database conserved domain classification, 128 GH5 enzymes have an architecture consisting of an N-terminal catalytic module, a CBM_X2 module and an unknown module of approximately 100 residues at the C-terminus (Supplementary Fig. 4B).	RESULTS
+125	141	catalytic module	structure_element	According to PFAM database conserved domain classification, 128 GH5 enzymes have an architecture consisting of an N-terminal catalytic module, a CBM_X2 module and an unknown module of approximately 100 residues at the C-terminus (Supplementary Fig. 4B).	RESULTS
+145	151	CBM_X2	structure_element	According to PFAM database conserved domain classification, 128 GH5 enzymes have an architecture consisting of an N-terminal catalytic module, a CBM_X2 module and an unknown module of approximately 100 residues at the C-terminus (Supplementary Fig. 4B).	RESULTS
+40	44	CBM1	structure_element	Of these, 12 enzymes have an additional CBM1, and 5 have a CBM2 at the N-terminal region.	RESULTS
+59	63	CBM2	structure_element	Of these, 12 enzymes have an additional CBM1, and 5 have a CBM2 at the N-terminal region.	RESULTS
+98	105	BlCel5B	protein	Based on this PFAM architecture and CAZy subfamily classification, all the 144 enzymes (including BlCel5B) belong to the GH5_4 subfamily and group together in the same branch of the phylogenetic tree, evidencing a common ancestor.	RESULTS
+121	126	GH5_4	protein_type	Based on this PFAM architecture and CAZy subfamily classification, all the 144 enzymes (including BlCel5B) belong to the GH5_4 subfamily and group together in the same branch of the phylogenetic tree, evidencing a common ancestor.	RESULTS
+182	199	phylogenetic tree	evidence	Based on this PFAM architecture and CAZy subfamily classification, all the 144 enzymes (including BlCel5B) belong to the GH5_4 subfamily and group together in the same branch of the phylogenetic tree, evidencing a common ancestor.	RESULTS
+217	222	CBM46	structure_element	These results support the hypothesis that the enzymes may employ the same mechanism by which ligand binding is mediated by an extensive conformational breathing of the enzyme that involves the large-scale movement of CBM46 around the Ig-like module (CBM_X2) as a structural hinge.	RESULTS
+234	248	Ig-like module	structure_element	These results support the hypothesis that the enzymes may employ the same mechanism by which ligand binding is mediated by an extensive conformational breathing of the enzyme that involves the large-scale movement of CBM46 around the Ig-like module (CBM_X2) as a structural hinge.	RESULTS
+250	256	CBM_X2	structure_element	These results support the hypothesis that the enzymes may employ the same mechanism by which ligand binding is mediated by an extensive conformational breathing of the enzyme that involves the large-scale movement of CBM46 around the Ig-like module (CBM_X2) as a structural hinge.	RESULTS
+263	279	structural hinge	structure_element	These results support the hypothesis that the enzymes may employ the same mechanism by which ligand binding is mediated by an extensive conformational breathing of the enzyme that involves the large-scale movement of CBM46 around the Ig-like module (CBM_X2) as a structural hinge.	RESULTS
+23	33	trimodular	protein_state	Here, we elucidate the trimodular molecular architecture of the full-length BlCel5B, a member of the GH5_4 subfamily, for which large-scale conformational dynamics appears to play a central role in its enzymatic activity.	DISCUSS
+64	75	full-length	protein_state	Here, we elucidate the trimodular molecular architecture of the full-length BlCel5B, a member of the GH5_4 subfamily, for which large-scale conformational dynamics appears to play a central role in its enzymatic activity.	DISCUSS
+76	83	BlCel5B	protein	Here, we elucidate the trimodular molecular architecture of the full-length BlCel5B, a member of the GH5_4 subfamily, for which large-scale conformational dynamics appears to play a central role in its enzymatic activity.	DISCUSS
+101	106	GH5_4	protein_type	Here, we elucidate the trimodular molecular architecture of the full-length BlCel5B, a member of the GH5_4 subfamily, for which large-scale conformational dynamics appears to play a central role in its enzymatic activity.	DISCUSS
+0	11	Full-length	protein_state	Full-length BlCel5B is active on both cellulosic and hemicellulosic substrates and auxiliary modules are crucial for its activity.	DISCUSS
+12	19	BlCel5B	protein	Full-length BlCel5B is active on both cellulosic and hemicellulosic substrates and auxiliary modules are crucial for its activity.	DISCUSS
+23	29	active	protein_state	Full-length BlCel5B is active on both cellulosic and hemicellulosic substrates and auxiliary modules are crucial for its activity.	DISCUSS
+38	48	cellulosic	chemical	Full-length BlCel5B is active on both cellulosic and hemicellulosic substrates and auxiliary modules are crucial for its activity.	DISCUSS
+53	67	hemicellulosic	chemical	Full-length BlCel5B is active on both cellulosic and hemicellulosic substrates and auxiliary modules are crucial for its activity.	DISCUSS
+5	32	carbohydrate-active enzymes	protein_type	Most carbohydrate-active enzymes are modular and consist of a catalytic domain appended to one or more separate AMs.	DISCUSS
+62	78	catalytic domain	structure_element	Most carbohydrate-active enzymes are modular and consist of a catalytic domain appended to one or more separate AMs.	DISCUSS
+112	115	AMs	structure_element	Most carbohydrate-active enzymes are modular and consist of a catalytic domain appended to one or more separate AMs.	DISCUSS
+0	3	AMs	structure_element	AMs, such as CBMs, typically recognize carbohydrates and target their cognate catalytic domains toward the substrate.	DISCUSS
+13	17	CBMs	structure_element	AMs, such as CBMs, typically recognize carbohydrates and target their cognate catalytic domains toward the substrate.	DISCUSS
+39	52	carbohydrates	chemical	AMs, such as CBMs, typically recognize carbohydrates and target their cognate catalytic domains toward the substrate.	DISCUSS
+78	95	catalytic domains	structure_element	AMs, such as CBMs, typically recognize carbohydrates and target their cognate catalytic domains toward the substrate.	DISCUSS
+12	31	structural analysis	experimental_method	Because the structural analysis of the protein is challenging if the linkers connecting the structural subunits of the enzyme are long and flexible, the standard approach is to study the domains separately.	DISCUSS
+69	76	linkers	structure_element	Because the structural analysis of the protein is challenging if the linkers connecting the structural subunits of the enzyme are long and flexible, the standard approach is to study the domains separately.	DISCUSS
+31	54	protein crystallography	experimental_method	In this work, a combination of protein crystallography, computational molecular dynamics, and SAXS analyses enabled the identification of a new conformational selection-based molecular mechanism that involves GH5 catalytic domain and two AMs in full-length BlCel5B.	DISCUSS
+56	88	computational molecular dynamics	experimental_method	In this work, a combination of protein crystallography, computational molecular dynamics, and SAXS analyses enabled the identification of a new conformational selection-based molecular mechanism that involves GH5 catalytic domain and two AMs in full-length BlCel5B.	DISCUSS
+94	98	SAXS	experimental_method	In this work, a combination of protein crystallography, computational molecular dynamics, and SAXS analyses enabled the identification of a new conformational selection-based molecular mechanism that involves GH5 catalytic domain and two AMs in full-length BlCel5B.	DISCUSS
+209	212	GH5	protein_type	In this work, a combination of protein crystallography, computational molecular dynamics, and SAXS analyses enabled the identification of a new conformational selection-based molecular mechanism that involves GH5 catalytic domain and two AMs in full-length BlCel5B.	DISCUSS
+213	229	catalytic domain	structure_element	In this work, a combination of protein crystallography, computational molecular dynamics, and SAXS analyses enabled the identification of a new conformational selection-based molecular mechanism that involves GH5 catalytic domain and two AMs in full-length BlCel5B.	DISCUSS
+238	241	AMs	structure_element	In this work, a combination of protein crystallography, computational molecular dynamics, and SAXS analyses enabled the identification of a new conformational selection-based molecular mechanism that involves GH5 catalytic domain and two AMs in full-length BlCel5B.	DISCUSS
+245	256	full-length	protein_state	In this work, a combination of protein crystallography, computational molecular dynamics, and SAXS analyses enabled the identification of a new conformational selection-based molecular mechanism that involves GH5 catalytic domain and two AMs in full-length BlCel5B.	DISCUSS
+257	264	BlCel5B	protein	In this work, a combination of protein crystallography, computational molecular dynamics, and SAXS analyses enabled the identification of a new conformational selection-based molecular mechanism that involves GH5 catalytic domain and two AMs in full-length BlCel5B.	DISCUSS
+21	28	BlCel5B	protein	We observed that the BlCel5B distal CBM46 is directly involved in shaping the local architecture of the substrate-binding site.	DISCUSS
+36	41	CBM46	structure_element	We observed that the BlCel5B distal CBM46 is directly involved in shaping the local architecture of the substrate-binding site.	DISCUSS
+104	126	substrate-binding site	site	We observed that the BlCel5B distal CBM46 is directly involved in shaping the local architecture of the substrate-binding site.	DISCUSS
+13	15	CD	structure_element	Although the CD alone appears unable to bind the substrate for catalysis, the AMs exhibit open-close motions that allow the substrate to be captured in a suitable position for hydrolysis.	DISCUSS
+16	21	alone	protein_state	Although the CD alone appears unable to bind the substrate for catalysis, the AMs exhibit open-close motions that allow the substrate to be captured in a suitable position for hydrolysis.	DISCUSS
+78	81	AMs	structure_element	Although the CD alone appears unable to bind the substrate for catalysis, the AMs exhibit open-close motions that allow the substrate to be captured in a suitable position for hydrolysis.	DISCUSS
+90	94	open	protein_state	Although the CD alone appears unable to bind the substrate for catalysis, the AMs exhibit open-close motions that allow the substrate to be captured in a suitable position for hydrolysis.	DISCUSS
+95	100	close	protein_state	Although the CD alone appears unable to bind the substrate for catalysis, the AMs exhibit open-close motions that allow the substrate to be captured in a suitable position for hydrolysis.	DISCUSS
+50	53	AMs	structure_element	Here, we advocate that large-amplitude motions of AMs are crucial for assembling the enzyme into its active conformation, highlighting a new function of CBMs.	DISCUSS
+101	107	active	protein_state	Here, we advocate that large-amplitude motions of AMs are crucial for assembling the enzyme into its active conformation, highlighting a new function of CBMs.	DISCUSS
+153	157	CBMs	structure_element	Here, we advocate that large-amplitude motions of AMs are crucial for assembling the enzyme into its active conformation, highlighting a new function of CBMs.	DISCUSS
+58	66	extended	protein_state	This mechanism of substrate binding closely resembles the extended conformational selection model, with the induced-fit mechanism of reaction as its limiting case.	DISCUSS
+96	98	GH	protein_type	To the best of our knowledge, this enzymatic mechanism has not been proposed previously for any GH.	DISCUSS
+4	19	CD binding site	site	The CD binding site of BlCel5B is open and relatively flat and is thus barely able to properly hold the substrate in position for catalysis without assistance from the CBM46.	DISCUSS
+23	30	BlCel5B	protein	The CD binding site of BlCel5B is open and relatively flat and is thus barely able to properly hold the substrate in position for catalysis without assistance from the CBM46.	DISCUSS
+168	173	CBM46	structure_element	The CD binding site of BlCel5B is open and relatively flat and is thus barely able to properly hold the substrate in position for catalysis without assistance from the CBM46.	DISCUSS
+19	23	GH5s	protein_type	In contrast, other GH5s belonging to subfamily 4 listed in the Protein Data Bank exhibit a deep binding cleft or tunnel that can effectively entrap the substrate for catalysis (Fig. 5).	DISCUSS
+96	109	binding cleft	site	In contrast, other GH5s belonging to subfamily 4 listed in the Protein Data Bank exhibit a deep binding cleft or tunnel that can effectively entrap the substrate for catalysis (Fig. 5).	DISCUSS
+113	119	tunnel	site	In contrast, other GH5s belonging to subfamily 4 listed in the Protein Data Bank exhibit a deep binding cleft or tunnel that can effectively entrap the substrate for catalysis (Fig. 5).	DISCUSS
+75	86	simulations	experimental_method	Due to the marked interdomain conformational rearrangement observed in our simulations, the CBM46 generates a confined binding site in BlCel5B that resembles the binding site architecture of the other GH5 enzymes that lack AMs.	DISCUSS
+92	97	CBM46	structure_element	Due to the marked interdomain conformational rearrangement observed in our simulations, the CBM46 generates a confined binding site in BlCel5B that resembles the binding site architecture of the other GH5 enzymes that lack AMs.	DISCUSS
+119	131	binding site	site	Due to the marked interdomain conformational rearrangement observed in our simulations, the CBM46 generates a confined binding site in BlCel5B that resembles the binding site architecture of the other GH5 enzymes that lack AMs.	DISCUSS
+135	142	BlCel5B	protein	Due to the marked interdomain conformational rearrangement observed in our simulations, the CBM46 generates a confined binding site in BlCel5B that resembles the binding site architecture of the other GH5 enzymes that lack AMs.	DISCUSS
+162	174	binding site	site	Due to the marked interdomain conformational rearrangement observed in our simulations, the CBM46 generates a confined binding site in BlCel5B that resembles the binding site architecture of the other GH5 enzymes that lack AMs.	DISCUSS
+201	204	GH5	protein_type	Due to the marked interdomain conformational rearrangement observed in our simulations, the CBM46 generates a confined binding site in BlCel5B that resembles the binding site architecture of the other GH5 enzymes that lack AMs.	DISCUSS
+218	222	lack	protein_state	Due to the marked interdomain conformational rearrangement observed in our simulations, the CBM46 generates a confined binding site in BlCel5B that resembles the binding site architecture of the other GH5 enzymes that lack AMs.	DISCUSS
+223	226	AMs	structure_element	Due to the marked interdomain conformational rearrangement observed in our simulations, the CBM46 generates a confined binding site in BlCel5B that resembles the binding site architecture of the other GH5 enzymes that lack AMs.	DISCUSS
+6	13	BlCel5B	protein	Thus, BlCel5B appears to have adopted a strategy of CBM46-mediated interactions for proper functioning.	DISCUSS
+52	57	CBM46	structure_element	Thus, BlCel5B appears to have adopted a strategy of CBM46-mediated interactions for proper functioning.	DISCUSS
+24	31	BhCel5B	protein	Although the homologous BhCel5B has the same domain architecture of BlCel5B and belongs to the same subfamily (a comparison of the sequence and structure of BlCel5B and BhCel5B is presented in Supplementary Fig. 5), its binding site exhibits important differences that may impact the catalytic mechanism.	DISCUSS
+68	75	BlCel5B	protein	Although the homologous BhCel5B has the same domain architecture of BlCel5B and belongs to the same subfamily (a comparison of the sequence and structure of BlCel5B and BhCel5B is presented in Supplementary Fig. 5), its binding site exhibits important differences that may impact the catalytic mechanism.	DISCUSS
+144	153	structure	evidence	Although the homologous BhCel5B has the same domain architecture of BlCel5B and belongs to the same subfamily (a comparison of the sequence and structure of BlCel5B and BhCel5B is presented in Supplementary Fig. 5), its binding site exhibits important differences that may impact the catalytic mechanism.	DISCUSS
+157	164	BlCel5B	protein	Although the homologous BhCel5B has the same domain architecture of BlCel5B and belongs to the same subfamily (a comparison of the sequence and structure of BlCel5B and BhCel5B is presented in Supplementary Fig. 5), its binding site exhibits important differences that may impact the catalytic mechanism.	DISCUSS
+169	176	BhCel5B	protein	Although the homologous BhCel5B has the same domain architecture of BlCel5B and belongs to the same subfamily (a comparison of the sequence and structure of BlCel5B and BhCel5B is presented in Supplementary Fig. 5), its binding site exhibits important differences that may impact the catalytic mechanism.	DISCUSS
+220	232	binding site	site	Although the homologous BhCel5B has the same domain architecture of BlCel5B and belongs to the same subfamily (a comparison of the sequence and structure of BlCel5B and BhCel5B is presented in Supplementary Fig. 5), its binding site exhibits important differences that may impact the catalytic mechanism.	DISCUSS
+4	11	BhCel5B	protein	The BhCel5B binding site is V-shaped and deeper than the BlCel5B binding site (Figs 5 and 6).	DISCUSS
+12	24	binding site	site	The BhCel5B binding site is V-shaped and deeper than the BlCel5B binding site (Figs 5 and 6).	DISCUSS
+28	36	V-shaped	protein_state	The BhCel5B binding site is V-shaped and deeper than the BlCel5B binding site (Figs 5 and 6).	DISCUSS
+57	64	BlCel5B	protein	The BhCel5B binding site is V-shaped and deeper than the BlCel5B binding site (Figs 5 and 6).	DISCUSS
+65	77	binding site	site	The BhCel5B binding site is V-shaped and deeper than the BlCel5B binding site (Figs 5 and 6).	DISCUSS
+19	23	loop	structure_element	This is due to the loop between residues F177 and R185 from BhCel5B (absent in the BlCel5B), which contains residue W181 that forms part of the binding cleft (Fig. 6).	DISCUSS
+41	45	F177	residue_name_number	This is due to the loop between residues F177 and R185 from BhCel5B (absent in the BlCel5B), which contains residue W181 that forms part of the binding cleft (Fig. 6).	DISCUSS
+50	54	R185	residue_name_number	This is due to the loop between residues F177 and R185 from BhCel5B (absent in the BlCel5B), which contains residue W181 that forms part of the binding cleft (Fig. 6).	DISCUSS
+60	67	BhCel5B	protein	This is due to the loop between residues F177 and R185 from BhCel5B (absent in the BlCel5B), which contains residue W181 that forms part of the binding cleft (Fig. 6).	DISCUSS
+69	75	absent	protein_state	This is due to the loop between residues F177 and R185 from BhCel5B (absent in the BlCel5B), which contains residue W181 that forms part of the binding cleft (Fig. 6).	DISCUSS
+83	90	BlCel5B	protein	This is due to the loop between residues F177 and R185 from BhCel5B (absent in the BlCel5B), which contains residue W181 that forms part of the binding cleft (Fig. 6).	DISCUSS
+116	120	W181	residue_name_number	This is due to the loop between residues F177 and R185 from BhCel5B (absent in the BlCel5B), which contains residue W181 that forms part of the binding cleft (Fig. 6).	DISCUSS
+144	157	binding cleft	site	This is due to the loop between residues F177 and R185 from BhCel5B (absent in the BlCel5B), which contains residue W181 that forms part of the binding cleft (Fig. 6).	DISCUSS
+23	30	BhCel5B	protein	Consistently, although BhCel5B CBM46 is important for β-1,3-1,4-glucan hydrolysis (BhCel5B is about 60-fold less active without CBM46), the truncated enzyme is completely active against xyloglucan, suggesting that the CBM46, in this case, is necessary for the binding to specific substrates.	DISCUSS
+31	36	CBM46	structure_element	Consistently, although BhCel5B CBM46 is important for β-1,3-1,4-glucan hydrolysis (BhCel5B is about 60-fold less active without CBM46), the truncated enzyme is completely active against xyloglucan, suggesting that the CBM46, in this case, is necessary for the binding to specific substrates.	DISCUSS
+54	70	β-1,3-1,4-glucan	chemical	Consistently, although BhCel5B CBM46 is important for β-1,3-1,4-glucan hydrolysis (BhCel5B is about 60-fold less active without CBM46), the truncated enzyme is completely active against xyloglucan, suggesting that the CBM46, in this case, is necessary for the binding to specific substrates.	DISCUSS
+83	90	BhCel5B	protein	Consistently, although BhCel5B CBM46 is important for β-1,3-1,4-glucan hydrolysis (BhCel5B is about 60-fold less active without CBM46), the truncated enzyme is completely active against xyloglucan, suggesting that the CBM46, in this case, is necessary for the binding to specific substrates.	DISCUSS
+113	119	active	protein_state	Consistently, although BhCel5B CBM46 is important for β-1,3-1,4-glucan hydrolysis (BhCel5B is about 60-fold less active without CBM46), the truncated enzyme is completely active against xyloglucan, suggesting that the CBM46, in this case, is necessary for the binding to specific substrates.	DISCUSS
+120	127	without	protein_state	Consistently, although BhCel5B CBM46 is important for β-1,3-1,4-glucan hydrolysis (BhCel5B is about 60-fold less active without CBM46), the truncated enzyme is completely active against xyloglucan, suggesting that the CBM46, in this case, is necessary for the binding to specific substrates.	DISCUSS
+128	133	CBM46	structure_element	Consistently, although BhCel5B CBM46 is important for β-1,3-1,4-glucan hydrolysis (BhCel5B is about 60-fold less active without CBM46), the truncated enzyme is completely active against xyloglucan, suggesting that the CBM46, in this case, is necessary for the binding to specific substrates.	DISCUSS
+140	149	truncated	protein_state	Consistently, although BhCel5B CBM46 is important for β-1,3-1,4-glucan hydrolysis (BhCel5B is about 60-fold less active without CBM46), the truncated enzyme is completely active against xyloglucan, suggesting that the CBM46, in this case, is necessary for the binding to specific substrates.	DISCUSS
+171	177	active	protein_state	Consistently, although BhCel5B CBM46 is important for β-1,3-1,4-glucan hydrolysis (BhCel5B is about 60-fold less active without CBM46), the truncated enzyme is completely active against xyloglucan, suggesting that the CBM46, in this case, is necessary for the binding to specific substrates.	DISCUSS
+186	196	xyloglucan	chemical	Consistently, although BhCel5B CBM46 is important for β-1,3-1,4-glucan hydrolysis (BhCel5B is about 60-fold less active without CBM46), the truncated enzyme is completely active against xyloglucan, suggesting that the CBM46, in this case, is necessary for the binding to specific substrates.	DISCUSS
+218	223	CBM46	structure_element	Consistently, although BhCel5B CBM46 is important for β-1,3-1,4-glucan hydrolysis (BhCel5B is about 60-fold less active without CBM46), the truncated enzyme is completely active against xyloglucan, suggesting that the CBM46, in this case, is necessary for the binding to specific substrates.	DISCUSS
+38	59	phylogenetic analysis	experimental_method	A closer inspection of results of the phylogenetic analysis, more specifically of the clade composed by GH5_4 enzymes with trimodular architecture (Supplementary Fig. 4C), reveals subclades whose main characteristic is the varying length of the loop located between residues 161 and 163 (BlCel5B residue numbering).	DISCUSS
+104	109	GH5_4	protein_type	A closer inspection of results of the phylogenetic analysis, more specifically of the clade composed by GH5_4 enzymes with trimodular architecture (Supplementary Fig. 4C), reveals subclades whose main characteristic is the varying length of the loop located between residues 161 and 163 (BlCel5B residue numbering).	DISCUSS
+123	133	trimodular	protein_state	A closer inspection of results of the phylogenetic analysis, more specifically of the clade composed by GH5_4 enzymes with trimodular architecture (Supplementary Fig. 4C), reveals subclades whose main characteristic is the varying length of the loop located between residues 161 and 163 (BlCel5B residue numbering).	DISCUSS
+245	249	loop	structure_element	A closer inspection of results of the phylogenetic analysis, more specifically of the clade composed by GH5_4 enzymes with trimodular architecture (Supplementary Fig. 4C), reveals subclades whose main characteristic is the varying length of the loop located between residues 161 and 163 (BlCel5B residue numbering).	DISCUSS
+275	286	161 and 163	residue_range	A closer inspection of results of the phylogenetic analysis, more specifically of the clade composed by GH5_4 enzymes with trimodular architecture (Supplementary Fig. 4C), reveals subclades whose main characteristic is the varying length of the loop located between residues 161 and 163 (BlCel5B residue numbering).	DISCUSS
+288	295	BlCel5B	protein	A closer inspection of results of the phylogenetic analysis, more specifically of the clade composed by GH5_4 enzymes with trimodular architecture (Supplementary Fig. 4C), reveals subclades whose main characteristic is the varying length of the loop located between residues 161 and 163 (BlCel5B residue numbering).	DISCUSS
+33	40	BlCel5B	protein	Therefore, our results show that BlCel5B represents a smaller group of enzymes that are completely dependent on its AMs for hydrolysis of plant cell wall polysaccharides, and that the underlying mechanism may rely on large-scale interdomain motions.	DISCUSS
+116	119	AMs	structure_element	Therefore, our results show that BlCel5B represents a smaller group of enzymes that are completely dependent on its AMs for hydrolysis of plant cell wall polysaccharides, and that the underlying mechanism may rely on large-scale interdomain motions.	DISCUSS
+138	143	plant	taxonomy_domain	Therefore, our results show that BlCel5B represents a smaller group of enzymes that are completely dependent on its AMs for hydrolysis of plant cell wall polysaccharides, and that the underlying mechanism may rely on large-scale interdomain motions.	DISCUSS
+154	169	polysaccharides	chemical	Therefore, our results show that BlCel5B represents a smaller group of enzymes that are completely dependent on its AMs for hydrolysis of plant cell wall polysaccharides, and that the underlying mechanism may rely on large-scale interdomain motions.	DISCUSS
+31	38	BlCel5B	protein	The amino acid sequence of the BlCel5B Ig-like module is recognized by BLASTP as belonging to CBM_X2, a poorly described group that has been compared with CBM-like accessory modules without a defined function.	DISCUSS
+39	53	Ig-like module	structure_element	The amino acid sequence of the BlCel5B Ig-like module is recognized by BLASTP as belonging to CBM_X2, a poorly described group that has been compared with CBM-like accessory modules without a defined function.	DISCUSS
+71	77	BLASTP	experimental_method	The amino acid sequence of the BlCel5B Ig-like module is recognized by BLASTP as belonging to CBM_X2, a poorly described group that has been compared with CBM-like accessory modules without a defined function.	DISCUSS
+94	100	CBM_X2	structure_element	The amino acid sequence of the BlCel5B Ig-like module is recognized by BLASTP as belonging to CBM_X2, a poorly described group that has been compared with CBM-like accessory modules without a defined function.	DISCUSS
+155	181	CBM-like accessory modules	structure_element	The amino acid sequence of the BlCel5B Ig-like module is recognized by BLASTP as belonging to CBM_X2, a poorly described group that has been compared with CBM-like accessory modules without a defined function.	DISCUSS
+26	33	BlCel5B	protein	Despite the similarity of BlCel5B Ig-like module to CBMs, it lacks an identifiable aromatic residue-rich carbohydrate-binding site.	DISCUSS
+34	48	Ig-like module	structure_element	Despite the similarity of BlCel5B Ig-like module to CBMs, it lacks an identifiable aromatic residue-rich carbohydrate-binding site.	DISCUSS
+52	56	CBMs	structure_element	Despite the similarity of BlCel5B Ig-like module to CBMs, it lacks an identifiable aromatic residue-rich carbohydrate-binding site.	DISCUSS
+105	130	carbohydrate-binding site	site	Despite the similarity of BlCel5B Ig-like module to CBMs, it lacks an identifiable aromatic residue-rich carbohydrate-binding site.	DISCUSS
+43	57	Ig-like module	structure_element	Nonetheless, according to our results, the Ig-like module seems to play an important function as a structural hinge, dynamically holding the CBM46 and CD in positions that are appropriate for enzymatic activity.	DISCUSS
+99	115	structural hinge	structure_element	Nonetheless, according to our results, the Ig-like module seems to play an important function as a structural hinge, dynamically holding the CBM46 and CD in positions that are appropriate for enzymatic activity.	DISCUSS
+141	146	CBM46	structure_element	Nonetheless, according to our results, the Ig-like module seems to play an important function as a structural hinge, dynamically holding the CBM46 and CD in positions that are appropriate for enzymatic activity.	DISCUSS
+151	153	CD	structure_element	Nonetheless, according to our results, the Ig-like module seems to play an important function as a structural hinge, dynamically holding the CBM46 and CD in positions that are appropriate for enzymatic activity.	DISCUSS
+28	65	crystallographic, computer simulation	experimental_method	Based on the results of our crystallographic, computer simulation, and SAXS structural analyses, as well as site-directed mutagenesis and activity assays, we propose a molecular mechanism for BlCel5B substrate binding, which might apply to other GH5_4 subfamily enzymes that share this tri-modular architecture.	DISCUSS
+71	95	SAXS structural analyses	experimental_method	Based on the results of our crystallographic, computer simulation, and SAXS structural analyses, as well as site-directed mutagenesis and activity assays, we propose a molecular mechanism for BlCel5B substrate binding, which might apply to other GH5_4 subfamily enzymes that share this tri-modular architecture.	DISCUSS
+108	133	site-directed mutagenesis	experimental_method	Based on the results of our crystallographic, computer simulation, and SAXS structural analyses, as well as site-directed mutagenesis and activity assays, we propose a molecular mechanism for BlCel5B substrate binding, which might apply to other GH5_4 subfamily enzymes that share this tri-modular architecture.	DISCUSS
+138	153	activity assays	experimental_method	Based on the results of our crystallographic, computer simulation, and SAXS structural analyses, as well as site-directed mutagenesis and activity assays, we propose a molecular mechanism for BlCel5B substrate binding, which might apply to other GH5_4 subfamily enzymes that share this tri-modular architecture.	DISCUSS
+192	199	BlCel5B	protein	Based on the results of our crystallographic, computer simulation, and SAXS structural analyses, as well as site-directed mutagenesis and activity assays, we propose a molecular mechanism for BlCel5B substrate binding, which might apply to other GH5_4 subfamily enzymes that share this tri-modular architecture.	DISCUSS
+246	251	GH5_4	protein_type	Based on the results of our crystallographic, computer simulation, and SAXS structural analyses, as well as site-directed mutagenesis and activity assays, we propose a molecular mechanism for BlCel5B substrate binding, which might apply to other GH5_4 subfamily enzymes that share this tri-modular architecture.	DISCUSS
+286	297	tri-modular	structure_element	Based on the results of our crystallographic, computer simulation, and SAXS structural analyses, as well as site-directed mutagenesis and activity assays, we propose a molecular mechanism for BlCel5B substrate binding, which might apply to other GH5_4 subfamily enzymes that share this tri-modular architecture.	DISCUSS
+0	7	BlCel5B	protein	BlCel5B can be found in several different conformational states ranging from CBM46/CD closed (or occluded) to extended conformations (Fig. 7).	DISCUSS
+77	82	CBM46	structure_element	BlCel5B can be found in several different conformational states ranging from CBM46/CD closed (or occluded) to extended conformations (Fig. 7).	DISCUSS
+83	85	CD	structure_element	BlCel5B can be found in several different conformational states ranging from CBM46/CD closed (or occluded) to extended conformations (Fig. 7).	DISCUSS
+86	92	closed	protein_state	BlCel5B can be found in several different conformational states ranging from CBM46/CD closed (or occluded) to extended conformations (Fig. 7).	DISCUSS
+97	105	occluded	protein_state	BlCel5B can be found in several different conformational states ranging from CBM46/CD closed (or occluded) to extended conformations (Fig. 7).	DISCUSS
+110	118	extended	protein_state	BlCel5B can be found in several different conformational states ranging from CBM46/CD closed (or occluded) to extended conformations (Fig. 7).	DISCUSS
+3	11	extended	protein_state	In extended configurations, the substrate may dock at the shallow substrate binding site of CD in one of the semi-closed conformations of the enzyme; however, its binding is properly stabilized for hydrolysis only with the aid of induced-fit repositioning mediated by CBM46.	DISCUSS
+66	88	substrate binding site	site	In extended configurations, the substrate may dock at the shallow substrate binding site of CD in one of the semi-closed conformations of the enzyme; however, its binding is properly stabilized for hydrolysis only with the aid of induced-fit repositioning mediated by CBM46.	DISCUSS
+92	94	CD	structure_element	In extended configurations, the substrate may dock at the shallow substrate binding site of CD in one of the semi-closed conformations of the enzyme; however, its binding is properly stabilized for hydrolysis only with the aid of induced-fit repositioning mediated by CBM46.	DISCUSS
+109	120	semi-closed	protein_state	In extended configurations, the substrate may dock at the shallow substrate binding site of CD in one of the semi-closed conformations of the enzyme; however, its binding is properly stabilized for hydrolysis only with the aid of induced-fit repositioning mediated by CBM46.	DISCUSS
+268	273	CBM46	structure_element	In extended configurations, the substrate may dock at the shallow substrate binding site of CD in one of the semi-closed conformations of the enzyme; however, its binding is properly stabilized for hydrolysis only with the aid of induced-fit repositioning mediated by CBM46.	DISCUSS
+42	49	BlCel5B	protein	After cleavage, the intrinsic dynamics of BlCel5B would eventually allow the opening of the active site for product release.	DISCUSS
+92	103	active site	site	After cleavage, the intrinsic dynamics of BlCel5B would eventually allow the opening of the active site for product release.	DISCUSS
+46	87	mutagenesis and enzymatic activity assays	experimental_method	The proposed mechanism is consistent with our mutagenesis and enzymatic activity assays, which show that the Ig-like module and CBM46 are indispensable for BlCel5B catalytic activity and, together with the CD, form the unique catalytic domain of the enzyme.	DISCUSS
+109	123	Ig-like module	structure_element	The proposed mechanism is consistent with our mutagenesis and enzymatic activity assays, which show that the Ig-like module and CBM46 are indispensable for BlCel5B catalytic activity and, together with the CD, form the unique catalytic domain of the enzyme.	DISCUSS
+128	133	CBM46	structure_element	The proposed mechanism is consistent with our mutagenesis and enzymatic activity assays, which show that the Ig-like module and CBM46 are indispensable for BlCel5B catalytic activity and, together with the CD, form the unique catalytic domain of the enzyme.	DISCUSS
+156	163	BlCel5B	protein	The proposed mechanism is consistent with our mutagenesis and enzymatic activity assays, which show that the Ig-like module and CBM46 are indispensable for BlCel5B catalytic activity and, together with the CD, form the unique catalytic domain of the enzyme.	DISCUSS
+206	208	CD	structure_element	The proposed mechanism is consistent with our mutagenesis and enzymatic activity assays, which show that the Ig-like module and CBM46 are indispensable for BlCel5B catalytic activity and, together with the CD, form the unique catalytic domain of the enzyme.	DISCUSS
+219	225	unique	protein_state	The proposed mechanism is consistent with our mutagenesis and enzymatic activity assays, which show that the Ig-like module and CBM46 are indispensable for BlCel5B catalytic activity and, together with the CD, form the unique catalytic domain of the enzyme.	DISCUSS
+226	242	catalytic domain	structure_element	The proposed mechanism is consistent with our mutagenesis and enzymatic activity assays, which show that the Ig-like module and CBM46 are indispensable for BlCel5B catalytic activity and, together with the CD, form the unique catalytic domain of the enzyme.	DISCUSS
+46	50	CBMs	structure_element	These experiments reveal a novel function for CBMs in which they are intimately involved in the assembly of the active site and catalytic process.	DISCUSS
+112	123	active site	site	These experiments reveal a novel function for CBMs in which they are intimately involved in the assembly of the active site and catalytic process.	DISCUSS
+0	20	Computer simulations	experimental_method	Computer simulations suggest that large-scale motions of the CBM46 and Ig-like domains mediate conformational selection and final induced-fit adjustments to trap the substrate at the active site and promote hydrolysis.	DISCUSS
+61	66	CBM46	structure_element	Computer simulations suggest that large-scale motions of the CBM46 and Ig-like domains mediate conformational selection and final induced-fit adjustments to trap the substrate at the active site and promote hydrolysis.	DISCUSS
+71	86	Ig-like domains	structure_element	Computer simulations suggest that large-scale motions of the CBM46 and Ig-like domains mediate conformational selection and final induced-fit adjustments to trap the substrate at the active site and promote hydrolysis.	DISCUSS
+183	194	active site	site	Computer simulations suggest that large-scale motions of the CBM46 and Ig-like domains mediate conformational selection and final induced-fit adjustments to trap the substrate at the active site and promote hydrolysis.	DISCUSS
+0	4	SAXS	experimental_method	SAXS data support the modeling results, providing compelling evidence for highly mobile domains in solution.	DISCUSS
+22	30	modeling	experimental_method	SAXS data support the modeling results, providing compelling evidence for highly mobile domains in solution.	DISCUSS
+74	87	highly mobile	protein_state	SAXS data support the modeling results, providing compelling evidence for highly mobile domains in solution.	DISCUSS
+9	17	spectrum	evidence	A single spectrum was obtained by averaging four independent spectra generated by 300 laser shots at 60% potency.	METHODS
+61	68	spectra	evidence	A single spectrum was obtained by averaging four independent spectra generated by 300 laser shots at 60% potency.	METHODS
+41	44	apo	protein_state	The missing residues were taken from the apo BlCel5B structure after structural alignment using the LovoAlign server.	METHODS
+0	20	BlCel5B-cellooctaose	complex_assembly	BlCel5B-cellooctaose	METHODS
+22	42	BlCel5B-cellooctaose	complex_assembly	To get a model of the BlCel5B-cellooctaose complex in the closed conformation, we took the configuration after 80 ns of the restrained 200-ns MD simulation as the starting point for a 500-ns-long restrained aMD simulation, in which the CBM46 moved towards the CD in the presence of the harmonically-restrained cellooctaose chain.	METHODS
+75	95	BlCel5B-cellooctaose	complex_assembly	After this procedure, we released the restraints and propagated the closed BlCel5B-cellooctaose complex for additional 500 ns of conventional, restraint-free MD simulation.	METHODS
+0	14	Crystal models	evidence	Crystal models of BlCel5B.	FIG
+18	25	BlCel5B	protein	Crystal models of BlCel5B.	FIG
+9	18	structure	evidence	Complete structure is shown as a cartoon illustration in (a) and a van der Waals surface in (b).	FIG
+4	6	CD	structure_element	The CD module (red) has a typical TIM-barrel fold, and its substrate-binding site is adjacent to CBM46 (blue).	FIG
+34	49	TIM-barrel fold	structure_element	The CD module (red) has a typical TIM-barrel fold, and its substrate-binding site is adjacent to CBM46 (blue).	FIG
+59	81	substrate-binding site	site	The CD module (red) has a typical TIM-barrel fold, and its substrate-binding site is adjacent to CBM46 (blue).	FIG
+97	102	CBM46	structure_element	The CD module (red) has a typical TIM-barrel fold, and its substrate-binding site is adjacent to CBM46 (blue).	FIG
+29	41	binding site	site	Despite the proximity of the binding site in the crystallographic model, the CBM46 residues W479 and W481 are distant from the substrate cellotetraose (yellow).	FIG
+77	82	CBM46	structure_element	Despite the proximity of the binding site in the crystallographic model, the CBM46 residues W479 and W481 are distant from the substrate cellotetraose (yellow).	FIG
+92	96	W479	residue_name_number	Despite the proximity of the binding site in the crystallographic model, the CBM46 residues W479 and W481 are distant from the substrate cellotetraose (yellow).	FIG
+101	105	W481	residue_name_number	Despite the proximity of the binding site in the crystallographic model, the CBM46 residues W479 and W481 are distant from the substrate cellotetraose (yellow).	FIG
+137	150	cellotetraose	chemical	Despite the proximity of the binding site in the crystallographic model, the CBM46 residues W479 and W481 are distant from the substrate cellotetraose (yellow).	FIG
+4	18	Ig-like domain	structure_element	The Ig-like domain (green) has a lateral position, serving as a connector between the CD and CBM46. (c) A superposition of the Ig-like domain and CBM46 illustrates their structural similarity, with most of the structural differences present in the loop highlighted by a red circle. (d) Cellotetraose occupies subsites -1 to -3 and is primarily coordinated by the residues represented in gray.	FIG
+86	88	CD	structure_element	The Ig-like domain (green) has a lateral position, serving as a connector between the CD and CBM46. (c) A superposition of the Ig-like domain and CBM46 illustrates their structural similarity, with most of the structural differences present in the loop highlighted by a red circle. (d) Cellotetraose occupies subsites -1 to -3 and is primarily coordinated by the residues represented in gray.	FIG
+93	98	CBM46	structure_element	The Ig-like domain (green) has a lateral position, serving as a connector between the CD and CBM46. (c) A superposition of the Ig-like domain and CBM46 illustrates their structural similarity, with most of the structural differences present in the loop highlighted by a red circle. (d) Cellotetraose occupies subsites -1 to -3 and is primarily coordinated by the residues represented in gray.	FIG
+106	119	superposition	experimental_method	The Ig-like domain (green) has a lateral position, serving as a connector between the CD and CBM46. (c) A superposition of the Ig-like domain and CBM46 illustrates their structural similarity, with most of the structural differences present in the loop highlighted by a red circle. (d) Cellotetraose occupies subsites -1 to -3 and is primarily coordinated by the residues represented in gray.	FIG
+127	141	Ig-like domain	structure_element	The Ig-like domain (green) has a lateral position, serving as a connector between the CD and CBM46. (c) A superposition of the Ig-like domain and CBM46 illustrates their structural similarity, with most of the structural differences present in the loop highlighted by a red circle. (d) Cellotetraose occupies subsites -1 to -3 and is primarily coordinated by the residues represented in gray.	FIG
+146	151	CBM46	structure_element	The Ig-like domain (green) has a lateral position, serving as a connector between the CD and CBM46. (c) A superposition of the Ig-like domain and CBM46 illustrates their structural similarity, with most of the structural differences present in the loop highlighted by a red circle. (d) Cellotetraose occupies subsites -1 to -3 and is primarily coordinated by the residues represented in gray.	FIG
+248	252	loop	structure_element	The Ig-like domain (green) has a lateral position, serving as a connector between the CD and CBM46. (c) A superposition of the Ig-like domain and CBM46 illustrates their structural similarity, with most of the structural differences present in the loop highlighted by a red circle. (d) Cellotetraose occupies subsites -1 to -3 and is primarily coordinated by the residues represented in gray.	FIG
+286	299	Cellotetraose	chemical	The Ig-like domain (green) has a lateral position, serving as a connector between the CD and CBM46. (c) A superposition of the Ig-like domain and CBM46 illustrates their structural similarity, with most of the structural differences present in the loop highlighted by a red circle. (d) Cellotetraose occupies subsites -1 to -3 and is primarily coordinated by the residues represented in gray.	FIG
+309	326	subsites -1 to -3	site	The Ig-like domain (green) has a lateral position, serving as a connector between the CD and CBM46. (c) A superposition of the Ig-like domain and CBM46 illustrates their structural similarity, with most of the structural differences present in the loop highlighted by a red circle. (d) Cellotetraose occupies subsites -1 to -3 and is primarily coordinated by the residues represented in gray.	FIG
+344	355	coordinated	bond_interaction	The Ig-like domain (green) has a lateral position, serving as a connector between the CD and CBM46. (c) A superposition of the Ig-like domain and CBM46 illustrates their structural similarity, with most of the structural differences present in the loop highlighted by a red circle. (d) Cellotetraose occupies subsites -1 to -3 and is primarily coordinated by the residues represented in gray.	FIG
+0	7	BlCel5B	protein	BlCel5B enzymatic activity characterization.	FIG
+8	43	enzymatic activity characterization	experimental_method	BlCel5B enzymatic activity characterization.	FIG
+4	16	MALDI/TOF-MS	experimental_method	(a) MALDI/TOF-MS spectra of the products released after incubation of BlCel5B and its two deletion constructs (ΔCBM46 and ΔIg-CBM46) with the substrate cellopentaose (C5).	FIG
+17	24	spectra	evidence	(a) MALDI/TOF-MS spectra of the products released after incubation of BlCel5B and its two deletion constructs (ΔCBM46 and ΔIg-CBM46) with the substrate cellopentaose (C5).	FIG
+70	77	BlCel5B	protein	(a) MALDI/TOF-MS spectra of the products released after incubation of BlCel5B and its two deletion constructs (ΔCBM46 and ΔIg-CBM46) with the substrate cellopentaose (C5).	FIG
+90	109	deletion constructs	experimental_method	(a) MALDI/TOF-MS spectra of the products released after incubation of BlCel5B and its two deletion constructs (ΔCBM46 and ΔIg-CBM46) with the substrate cellopentaose (C5).	FIG
+111	117	ΔCBM46	mutant	(a) MALDI/TOF-MS spectra of the products released after incubation of BlCel5B and its two deletion constructs (ΔCBM46 and ΔIg-CBM46) with the substrate cellopentaose (C5).	FIG
+122	131	ΔIg-CBM46	mutant	(a) MALDI/TOF-MS spectra of the products released after incubation of BlCel5B and its two deletion constructs (ΔCBM46 and ΔIg-CBM46) with the substrate cellopentaose (C5).	FIG
+152	165	cellopentaose	chemical	(a) MALDI/TOF-MS spectra of the products released after incubation of BlCel5B and its two deletion constructs (ΔCBM46 and ΔIg-CBM46) with the substrate cellopentaose (C5).	FIG
+167	169	C5	chemical	(a) MALDI/TOF-MS spectra of the products released after incubation of BlCel5B and its two deletion constructs (ΔCBM46 and ΔIg-CBM46) with the substrate cellopentaose (C5).	FIG
+16	23	spectra	evidence	The first three spectra show the substrate, enzyme and buffer controls.	FIG
+10	18	spectrum	evidence	The forth spectrum reveals that full length BlCel5B is capable of enzymatic hydrolysis of C5 into smaller oligosaccharides such as C4, C3 and C2.	FIG
+32	43	full length	protein_state	The forth spectrum reveals that full length BlCel5B is capable of enzymatic hydrolysis of C5 into smaller oligosaccharides such as C4, C3 and C2.	FIG
+44	51	BlCel5B	protein	The forth spectrum reveals that full length BlCel5B is capable of enzymatic hydrolysis of C5 into smaller oligosaccharides such as C4, C3 and C2.	FIG
+90	92	C5	chemical	The forth spectrum reveals that full length BlCel5B is capable of enzymatic hydrolysis of C5 into smaller oligosaccharides such as C4, C3 and C2.	FIG
+106	122	oligosaccharides	chemical	The forth spectrum reveals that full length BlCel5B is capable of enzymatic hydrolysis of C5 into smaller oligosaccharides such as C4, C3 and C2.	FIG
+131	133	C4	chemical	The forth spectrum reveals that full length BlCel5B is capable of enzymatic hydrolysis of C5 into smaller oligosaccharides such as C4, C3 and C2.	FIG
+135	137	C3	chemical	The forth spectrum reveals that full length BlCel5B is capable of enzymatic hydrolysis of C5 into smaller oligosaccharides such as C4, C3 and C2.	FIG
+142	144	C2	chemical	The forth spectrum reveals that full length BlCel5B is capable of enzymatic hydrolysis of C5 into smaller oligosaccharides such as C4, C3 and C2.	FIG
+13	20	spectra	evidence	The last two spectra show that the C-terminal deletions eliminate the enzyme activity.	FIG
+56	85	eliminate the enzyme activity	protein_state	The last two spectra show that the C-terminal deletions eliminate the enzyme activity.	FIG
+0	7	BlCel5B	protein	BlCel5B activities on CMC as functions of pH and temperature are shown in (b) and (c), respectively.	FIG
+22	25	CMC	chemical	BlCel5B activities on CMC as functions of pH and temperature are shown in (b) and (c), respectively.	FIG
+4	26	Michaelis-Menten curve	evidence	(d) Michaelis-Menten curve using CMC as a substrate.	FIG
+33	36	CMC	chemical	(d) Michaelis-Menten curve using CMC as a substrate.	FIG
+0	4	Open	protein_state	Open-close transitions of BlCel5B.	FIG
+5	10	close	protein_state	Open-close transitions of BlCel5B.	FIG
+26	33	BlCel5B	protein	Open-close transitions of BlCel5B.	FIG
+4	11	BlCel5B	protein	(a) BlCel5B in the absence of substrate and (b) in the presence of cellooctaose, as observed in our aMD simulations.	FIG
+19	29	absence of	protein_state	(a) BlCel5B in the absence of substrate and (b) in the presence of cellooctaose, as observed in our aMD simulations.	FIG
+55	66	presence of	protein_state	(a) BlCel5B in the absence of substrate and (b) in the presence of cellooctaose, as observed in our aMD simulations.	FIG
+67	79	cellooctaose	chemical	(a) BlCel5B in the absence of substrate and (b) in the presence of cellooctaose, as observed in our aMD simulations.	FIG
+100	115	aMD simulations	experimental_method	(a) BlCel5B in the absence of substrate and (b) in the presence of cellooctaose, as observed in our aMD simulations.	FIG
+4	12	distance	evidence	The distance between the α carbon of residues I120 (CD) and E477 (CBM46), illustrated as spheres in (a), is plotted in (c), revealing a transition by the decrease in the distance from 40 Å to 7 Å (substrate-free) or 20 Å (in presence of cellooctaose).	FIG
+46	50	I120	residue_name_number	The distance between the α carbon of residues I120 (CD) and E477 (CBM46), illustrated as spheres in (a), is plotted in (c), revealing a transition by the decrease in the distance from 40 Å to 7 Å (substrate-free) or 20 Å (in presence of cellooctaose).	FIG
+52	54	CD	structure_element	The distance between the α carbon of residues I120 (CD) and E477 (CBM46), illustrated as spheres in (a), is plotted in (c), revealing a transition by the decrease in the distance from 40 Å to 7 Å (substrate-free) or 20 Å (in presence of cellooctaose).	FIG
+60	64	E477	residue_name_number	The distance between the α carbon of residues I120 (CD) and E477 (CBM46), illustrated as spheres in (a), is plotted in (c), revealing a transition by the decrease in the distance from 40 Å to 7 Å (substrate-free) or 20 Å (in presence of cellooctaose).	FIG
+66	71	CBM46	structure_element	The distance between the α carbon of residues I120 (CD) and E477 (CBM46), illustrated as spheres in (a), is plotted in (c), revealing a transition by the decrease in the distance from 40 Å to 7 Å (substrate-free) or 20 Å (in presence of cellooctaose).	FIG
+170	178	distance	evidence	The distance between the α carbon of residues I120 (CD) and E477 (CBM46), illustrated as spheres in (a), is plotted in (c), revealing a transition by the decrease in the distance from 40 Å to 7 Å (substrate-free) or 20 Å (in presence of cellooctaose).	FIG
+197	211	substrate-free	protein_state	The distance between the α carbon of residues I120 (CD) and E477 (CBM46), illustrated as spheres in (a), is plotted in (c), revealing a transition by the decrease in the distance from 40 Å to 7 Å (substrate-free) or 20 Å (in presence of cellooctaose).	FIG
+225	236	presence of	protein_state	The distance between the α carbon of residues I120 (CD) and E477 (CBM46), illustrated as spheres in (a), is plotted in (c), revealing a transition by the decrease in the distance from 40 Å to 7 Å (substrate-free) or 20 Å (in presence of cellooctaose).	FIG
+237	249	cellooctaose	chemical	The distance between the α carbon of residues I120 (CD) and E477 (CBM46), illustrated as spheres in (a), is plotted in (c), revealing a transition by the decrease in the distance from 40 Å to 7 Å (substrate-free) or 20 Å (in presence of cellooctaose).	FIG
+8	22	substrate-free	protein_state	For the substrate-free enzyme, the red line refers to a 1 μs-long aMD; for the BlCel5B-cellooctaose complex, the first 500 ns refers to aMD (in blue) and the second 500 ns to conventional MD (in turquoise).	FIG
+66	69	aMD	experimental_method	For the substrate-free enzyme, the red line refers to a 1 μs-long aMD; for the BlCel5B-cellooctaose complex, the first 500 ns refers to aMD (in blue) and the second 500 ns to conventional MD (in turquoise).	FIG
+79	99	BlCel5B-cellooctaose	complex_assembly	For the substrate-free enzyme, the red line refers to a 1 μs-long aMD; for the BlCel5B-cellooctaose complex, the first 500 ns refers to aMD (in blue) and the second 500 ns to conventional MD (in turquoise).	FIG
+136	139	aMD	experimental_method	For the substrate-free enzyme, the red line refers to a 1 μs-long aMD; for the BlCel5B-cellooctaose complex, the first 500 ns refers to aMD (in blue) and the second 500 ns to conventional MD (in turquoise).	FIG
+188	190	MD	experimental_method	For the substrate-free enzyme, the red line refers to a 1 μs-long aMD; for the BlCel5B-cellooctaose complex, the first 500 ns refers to aMD (in blue) and the second 500 ns to conventional MD (in turquoise).	FIG
+22	42	BlCel5B-cellooctaose	complex_assembly	(d) A snapshot of the BlCel5B-cellooctaose complex, highlighting the tryptophan residues that interact with the glucan chain in subsites −4 to +4.	FIG
+69	79	tryptophan	residue_name	(d) A snapshot of the BlCel5B-cellooctaose complex, highlighting the tryptophan residues that interact with the glucan chain in subsites −4 to +4.	FIG
+112	118	glucan	chemical	(d) A snapshot of the BlCel5B-cellooctaose complex, highlighting the tryptophan residues that interact with the glucan chain in subsites −4 to +4.	FIG
+128	145	subsites −4 to +4	site	(d) A snapshot of the BlCel5B-cellooctaose complex, highlighting the tryptophan residues that interact with the glucan chain in subsites −4 to +4.	FIG
+9	13	W479	residue_name_number	Residues W479 and W481 belong to CBM46 and only become available for substrate interactions in the closed configuration of BlCel5B.	FIG
+18	22	W481	residue_name_number	Residues W479 and W481 belong to CBM46 and only become available for substrate interactions in the closed configuration of BlCel5B.	FIG
+33	38	CBM46	structure_element	Residues W479 and W481 belong to CBM46 and only become available for substrate interactions in the closed configuration of BlCel5B.	FIG
+99	105	closed	protein_state	Residues W479 and W481 belong to CBM46 and only become available for substrate interactions in the closed configuration of BlCel5B.	FIG
+123	130	BlCel5B	protein	Residues W479 and W481 belong to CBM46 and only become available for substrate interactions in the closed configuration of BlCel5B.	FIG
+25	32	BlCel5B	protein	Large-scale movements of BlCel5B modules and superposition of their representative conformations with the SAXS envelope.	FIG
+45	58	superposition	experimental_method	Large-scale movements of BlCel5B modules and superposition of their representative conformations with the SAXS envelope.	FIG
+106	110	SAXS	experimental_method	Large-scale movements of BlCel5B modules and superposition of their representative conformations with the SAXS envelope.	FIG
+111	119	envelope	evidence	Large-scale movements of BlCel5B modules and superposition of their representative conformations with the SAXS envelope.	FIG
+4	11	BlCel5B	protein	(a) BlCel5B structure showing the distance between the backbone beads of residues I120 and E477, which are centrally located in CD and CBM46, respectively, as a metric for the relative disposition between the two domains. (b) Time history of the I120-E477 distance computed using CG-MD simulations.	FIG
+12	21	structure	evidence	(a) BlCel5B structure showing the distance between the backbone beads of residues I120 and E477, which are centrally located in CD and CBM46, respectively, as a metric for the relative disposition between the two domains. (b) Time history of the I120-E477 distance computed using CG-MD simulations.	FIG
+34	42	distance	evidence	(a) BlCel5B structure showing the distance between the backbone beads of residues I120 and E477, which are centrally located in CD and CBM46, respectively, as a metric for the relative disposition between the two domains. (b) Time history of the I120-E477 distance computed using CG-MD simulations.	FIG
+82	86	I120	residue_name_number	(a) BlCel5B structure showing the distance between the backbone beads of residues I120 and E477, which are centrally located in CD and CBM46, respectively, as a metric for the relative disposition between the two domains. (b) Time history of the I120-E477 distance computed using CG-MD simulations.	FIG
+91	95	E477	residue_name_number	(a) BlCel5B structure showing the distance between the backbone beads of residues I120 and E477, which are centrally located in CD and CBM46, respectively, as a metric for the relative disposition between the two domains. (b) Time history of the I120-E477 distance computed using CG-MD simulations.	FIG
+128	130	CD	structure_element	(a) BlCel5B structure showing the distance between the backbone beads of residues I120 and E477, which are centrally located in CD and CBM46, respectively, as a metric for the relative disposition between the two domains. (b) Time history of the I120-E477 distance computed using CG-MD simulations.	FIG
+135	140	CBM46	structure_element	(a) BlCel5B structure showing the distance between the backbone beads of residues I120 and E477, which are centrally located in CD and CBM46, respectively, as a metric for the relative disposition between the two domains. (b) Time history of the I120-E477 distance computed using CG-MD simulations.	FIG
+246	250	I120	residue_name_number	(a) BlCel5B structure showing the distance between the backbone beads of residues I120 and E477, which are centrally located in CD and CBM46, respectively, as a metric for the relative disposition between the two domains. (b) Time history of the I120-E477 distance computed using CG-MD simulations.	FIG
+251	255	E477	residue_name_number	(a) BlCel5B structure showing the distance between the backbone beads of residues I120 and E477, which are centrally located in CD and CBM46, respectively, as a metric for the relative disposition between the two domains. (b) Time history of the I120-E477 distance computed using CG-MD simulations.	FIG
+256	264	distance	evidence	(a) BlCel5B structure showing the distance between the backbone beads of residues I120 and E477, which are centrally located in CD and CBM46, respectively, as a metric for the relative disposition between the two domains. (b) Time history of the I120-E477 distance computed using CG-MD simulations.	FIG
+280	297	CG-MD simulations	experimental_method	(a) BlCel5B structure showing the distance between the backbone beads of residues I120 and E477, which are centrally located in CD and CBM46, respectively, as a metric for the relative disposition between the two domains. (b) Time history of the I120-E477 distance computed using CG-MD simulations.	FIG
+71	82	simulations	experimental_method	Different colors separated by vertical lines correspond to independent simulations of approximately 120 μs. (c) The distance distribution indicates three major peaks: closed or occluded CBM46/CD conformations (I); semi-open (II), which is similar to the crystallographic structure; and extended conformers (III).	FIG
+116	137	distance distribution	evidence	Different colors separated by vertical lines correspond to independent simulations of approximately 120 μs. (c) The distance distribution indicates three major peaks: closed or occluded CBM46/CD conformations (I); semi-open (II), which is similar to the crystallographic structure; and extended conformers (III).	FIG
+167	173	closed	protein_state	Different colors separated by vertical lines correspond to independent simulations of approximately 120 μs. (c) The distance distribution indicates three major peaks: closed or occluded CBM46/CD conformations (I); semi-open (II), which is similar to the crystallographic structure; and extended conformers (III).	FIG
+177	185	occluded	protein_state	Different colors separated by vertical lines correspond to independent simulations of approximately 120 μs. (c) The distance distribution indicates three major peaks: closed or occluded CBM46/CD conformations (I); semi-open (II), which is similar to the crystallographic structure; and extended conformers (III).	FIG
+186	191	CBM46	structure_element	Different colors separated by vertical lines correspond to independent simulations of approximately 120 μs. (c) The distance distribution indicates three major peaks: closed or occluded CBM46/CD conformations (I); semi-open (II), which is similar to the crystallographic structure; and extended conformers (III).	FIG
+192	194	CD	structure_element	Different colors separated by vertical lines correspond to independent simulations of approximately 120 μs. (c) The distance distribution indicates three major peaks: closed or occluded CBM46/CD conformations (I); semi-open (II), which is similar to the crystallographic structure; and extended conformers (III).	FIG
+214	223	semi-open	protein_state	Different colors separated by vertical lines correspond to independent simulations of approximately 120 μs. (c) The distance distribution indicates three major peaks: closed or occluded CBM46/CD conformations (I); semi-open (II), which is similar to the crystallographic structure; and extended conformers (III).	FIG
+254	280	crystallographic structure	evidence	Different colors separated by vertical lines correspond to independent simulations of approximately 120 μs. (c) The distance distribution indicates three major peaks: closed or occluded CBM46/CD conformations (I); semi-open (II), which is similar to the crystallographic structure; and extended conformers (III).	FIG
+286	294	extended	protein_state	Different colors separated by vertical lines correspond to independent simulations of approximately 120 μs. (c) The distance distribution indicates three major peaks: closed or occluded CBM46/CD conformations (I); semi-open (II), which is similar to the crystallographic structure; and extended conformers (III).	FIG
+4	19	Superimposition	experimental_method	(d) Superimposition of the three representative molecular conformations of BlCel5B with the SAXS model. (e) Average structures obtained from the simulation segments corresponding to population groups I-III, which are individually superposed on the SAXS envelope.	FIG
+75	82	BlCel5B	protein	(d) Superimposition of the three representative molecular conformations of BlCel5B with the SAXS model. (e) Average structures obtained from the simulation segments corresponding to population groups I-III, which are individually superposed on the SAXS envelope.	FIG
+92	96	SAXS	experimental_method	(d) Superimposition of the three representative molecular conformations of BlCel5B with the SAXS model. (e) Average structures obtained from the simulation segments corresponding to population groups I-III, which are individually superposed on the SAXS envelope.	FIG
+97	102	model	evidence	(d) Superimposition of the three representative molecular conformations of BlCel5B with the SAXS model. (e) Average structures obtained from the simulation segments corresponding to population groups I-III, which are individually superposed on the SAXS envelope.	FIG
+116	126	structures	evidence	(d) Superimposition of the three representative molecular conformations of BlCel5B with the SAXS model. (e) Average structures obtained from the simulation segments corresponding to population groups I-III, which are individually superposed on the SAXS envelope.	FIG
+145	155	simulation	experimental_method	(d) Superimposition of the three representative molecular conformations of BlCel5B with the SAXS model. (e) Average structures obtained from the simulation segments corresponding to population groups I-III, which are individually superposed on the SAXS envelope.	FIG
+230	240	superposed	experimental_method	(d) Superimposition of the three representative molecular conformations of BlCel5B with the SAXS model. (e) Average structures obtained from the simulation segments corresponding to population groups I-III, which are individually superposed on the SAXS envelope.	FIG
+248	252	SAXS	experimental_method	(d) Superimposition of the three representative molecular conformations of BlCel5B with the SAXS model. (e) Average structures obtained from the simulation segments corresponding to population groups I-III, which are individually superposed on the SAXS envelope.	FIG
+253	261	envelope	evidence	(d) Superimposition of the three representative molecular conformations of BlCel5B with the SAXS model. (e) Average structures obtained from the simulation segments corresponding to population groups I-III, which are individually superposed on the SAXS envelope.	FIG
+0	10	Comparison	experimental_method	Comparison of the binding site shape of GH5_4 enzymes available on the Protein Data Bank.	FIG
+18	30	binding site	site	Comparison of the binding site shape of GH5_4 enzymes available on the Protein Data Bank.	FIG
+40	45	GH5_4	protein_type	Comparison of the binding site shape of GH5_4 enzymes available on the Protein Data Bank.	FIG
+4	11	BlCel5B	protein	(a) BlCel5B in the crystallographic and closed configuration; (b) Bacillus halodurans Cel5B (BhCel5B) (PDB id: 4V2X) (c) Piromyces rhizinflata GH5 endoglucanase (PDB id: 3AYR); (d) Clostridium cellulolyticum GH5 endoglucanase (PDB id: 1EDG); (e) Clostridium cellulovorans GH5 endoglucanase (PDB id: 3NDY); (f) Bacteroides ovatus GH5 xyloglucanase (PDB id: 3ZMR); (g) Paenibacillus pabuli GH5 xyloglucanase (PDB id: 2JEP); (h) Prevotella bryantii GH5 endoglucanase (PDB id: 3VDH); (i) Ruminiclostridium thermocellum multifunctional GH5 cellulase, xylanase and mannase (PDB id: 4IM4); (j) Bacteroidetes bacterium AC2a endocellulase (PDB id: 4YHE).	FIG
+19	35	crystallographic	experimental_method	(a) BlCel5B in the crystallographic and closed configuration; (b) Bacillus halodurans Cel5B (BhCel5B) (PDB id: 4V2X) (c) Piromyces rhizinflata GH5 endoglucanase (PDB id: 3AYR); (d) Clostridium cellulolyticum GH5 endoglucanase (PDB id: 1EDG); (e) Clostridium cellulovorans GH5 endoglucanase (PDB id: 3NDY); (f) Bacteroides ovatus GH5 xyloglucanase (PDB id: 3ZMR); (g) Paenibacillus pabuli GH5 xyloglucanase (PDB id: 2JEP); (h) Prevotella bryantii GH5 endoglucanase (PDB id: 3VDH); (i) Ruminiclostridium thermocellum multifunctional GH5 cellulase, xylanase and mannase (PDB id: 4IM4); (j) Bacteroidetes bacterium AC2a endocellulase (PDB id: 4YHE).	FIG
+40	46	closed	protein_state	(a) BlCel5B in the crystallographic and closed configuration; (b) Bacillus halodurans Cel5B (BhCel5B) (PDB id: 4V2X) (c) Piromyces rhizinflata GH5 endoglucanase (PDB id: 3AYR); (d) Clostridium cellulolyticum GH5 endoglucanase (PDB id: 1EDG); (e) Clostridium cellulovorans GH5 endoglucanase (PDB id: 3NDY); (f) Bacteroides ovatus GH5 xyloglucanase (PDB id: 3ZMR); (g) Paenibacillus pabuli GH5 xyloglucanase (PDB id: 2JEP); (h) Prevotella bryantii GH5 endoglucanase (PDB id: 3VDH); (i) Ruminiclostridium thermocellum multifunctional GH5 cellulase, xylanase and mannase (PDB id: 4IM4); (j) Bacteroidetes bacterium AC2a endocellulase (PDB id: 4YHE).	FIG
+66	85	Bacillus halodurans	species	(a) BlCel5B in the crystallographic and closed configuration; (b) Bacillus halodurans Cel5B (BhCel5B) (PDB id: 4V2X) (c) Piromyces rhizinflata GH5 endoglucanase (PDB id: 3AYR); (d) Clostridium cellulolyticum GH5 endoglucanase (PDB id: 1EDG); (e) Clostridium cellulovorans GH5 endoglucanase (PDB id: 3NDY); (f) Bacteroides ovatus GH5 xyloglucanase (PDB id: 3ZMR); (g) Paenibacillus pabuli GH5 xyloglucanase (PDB id: 2JEP); (h) Prevotella bryantii GH5 endoglucanase (PDB id: 3VDH); (i) Ruminiclostridium thermocellum multifunctional GH5 cellulase, xylanase and mannase (PDB id: 4IM4); (j) Bacteroidetes bacterium AC2a endocellulase (PDB id: 4YHE).	FIG
+86	91	Cel5B	protein	(a) BlCel5B in the crystallographic and closed configuration; (b) Bacillus halodurans Cel5B (BhCel5B) (PDB id: 4V2X) (c) Piromyces rhizinflata GH5 endoglucanase (PDB id: 3AYR); (d) Clostridium cellulolyticum GH5 endoglucanase (PDB id: 1EDG); (e) Clostridium cellulovorans GH5 endoglucanase (PDB id: 3NDY); (f) Bacteroides ovatus GH5 xyloglucanase (PDB id: 3ZMR); (g) Paenibacillus pabuli GH5 xyloglucanase (PDB id: 2JEP); (h) Prevotella bryantii GH5 endoglucanase (PDB id: 3VDH); (i) Ruminiclostridium thermocellum multifunctional GH5 cellulase, xylanase and mannase (PDB id: 4IM4); (j) Bacteroidetes bacterium AC2a endocellulase (PDB id: 4YHE).	FIG
+93	100	BhCel5B	protein	(a) BlCel5B in the crystallographic and closed configuration; (b) Bacillus halodurans Cel5B (BhCel5B) (PDB id: 4V2X) (c) Piromyces rhizinflata GH5 endoglucanase (PDB id: 3AYR); (d) Clostridium cellulolyticum GH5 endoglucanase (PDB id: 1EDG); (e) Clostridium cellulovorans GH5 endoglucanase (PDB id: 3NDY); (f) Bacteroides ovatus GH5 xyloglucanase (PDB id: 3ZMR); (g) Paenibacillus pabuli GH5 xyloglucanase (PDB id: 2JEP); (h) Prevotella bryantii GH5 endoglucanase (PDB id: 3VDH); (i) Ruminiclostridium thermocellum multifunctional GH5 cellulase, xylanase and mannase (PDB id: 4IM4); (j) Bacteroidetes bacterium AC2a endocellulase (PDB id: 4YHE).	FIG
+121	142	Piromyces rhizinflata	species	(a) BlCel5B in the crystallographic and closed configuration; (b) Bacillus halodurans Cel5B (BhCel5B) (PDB id: 4V2X) (c) Piromyces rhizinflata GH5 endoglucanase (PDB id: 3AYR); (d) Clostridium cellulolyticum GH5 endoglucanase (PDB id: 1EDG); (e) Clostridium cellulovorans GH5 endoglucanase (PDB id: 3NDY); (f) Bacteroides ovatus GH5 xyloglucanase (PDB id: 3ZMR); (g) Paenibacillus pabuli GH5 xyloglucanase (PDB id: 2JEP); (h) Prevotella bryantii GH5 endoglucanase (PDB id: 3VDH); (i) Ruminiclostridium thermocellum multifunctional GH5 cellulase, xylanase and mannase (PDB id: 4IM4); (j) Bacteroidetes bacterium AC2a endocellulase (PDB id: 4YHE).	FIG
+143	146	GH5	protein_type	(a) BlCel5B in the crystallographic and closed configuration; (b) Bacillus halodurans Cel5B (BhCel5B) (PDB id: 4V2X) (c) Piromyces rhizinflata GH5 endoglucanase (PDB id: 3AYR); (d) Clostridium cellulolyticum GH5 endoglucanase (PDB id: 1EDG); (e) Clostridium cellulovorans GH5 endoglucanase (PDB id: 3NDY); (f) Bacteroides ovatus GH5 xyloglucanase (PDB id: 3ZMR); (g) Paenibacillus pabuli GH5 xyloglucanase (PDB id: 2JEP); (h) Prevotella bryantii GH5 endoglucanase (PDB id: 3VDH); (i) Ruminiclostridium thermocellum multifunctional GH5 cellulase, xylanase and mannase (PDB id: 4IM4); (j) Bacteroidetes bacterium AC2a endocellulase (PDB id: 4YHE).	FIG
+147	160	endoglucanase	protein_type	(a) BlCel5B in the crystallographic and closed configuration; (b) Bacillus halodurans Cel5B (BhCel5B) (PDB id: 4V2X) (c) Piromyces rhizinflata GH5 endoglucanase (PDB id: 3AYR); (d) Clostridium cellulolyticum GH5 endoglucanase (PDB id: 1EDG); (e) Clostridium cellulovorans GH5 endoglucanase (PDB id: 3NDY); (f) Bacteroides ovatus GH5 xyloglucanase (PDB id: 3ZMR); (g) Paenibacillus pabuli GH5 xyloglucanase (PDB id: 2JEP); (h) Prevotella bryantii GH5 endoglucanase (PDB id: 3VDH); (i) Ruminiclostridium thermocellum multifunctional GH5 cellulase, xylanase and mannase (PDB id: 4IM4); (j) Bacteroidetes bacterium AC2a endocellulase (PDB id: 4YHE).	FIG
+181	207	Clostridium cellulolyticum	species	(a) BlCel5B in the crystallographic and closed configuration; (b) Bacillus halodurans Cel5B (BhCel5B) (PDB id: 4V2X) (c) Piromyces rhizinflata GH5 endoglucanase (PDB id: 3AYR); (d) Clostridium cellulolyticum GH5 endoglucanase (PDB id: 1EDG); (e) Clostridium cellulovorans GH5 endoglucanase (PDB id: 3NDY); (f) Bacteroides ovatus GH5 xyloglucanase (PDB id: 3ZMR); (g) Paenibacillus pabuli GH5 xyloglucanase (PDB id: 2JEP); (h) Prevotella bryantii GH5 endoglucanase (PDB id: 3VDH); (i) Ruminiclostridium thermocellum multifunctional GH5 cellulase, xylanase and mannase (PDB id: 4IM4); (j) Bacteroidetes bacterium AC2a endocellulase (PDB id: 4YHE).	FIG
+208	211	GH5	protein_type	(a) BlCel5B in the crystallographic and closed configuration; (b) Bacillus halodurans Cel5B (BhCel5B) (PDB id: 4V2X) (c) Piromyces rhizinflata GH5 endoglucanase (PDB id: 3AYR); (d) Clostridium cellulolyticum GH5 endoglucanase (PDB id: 1EDG); (e) Clostridium cellulovorans GH5 endoglucanase (PDB id: 3NDY); (f) Bacteroides ovatus GH5 xyloglucanase (PDB id: 3ZMR); (g) Paenibacillus pabuli GH5 xyloglucanase (PDB id: 2JEP); (h) Prevotella bryantii GH5 endoglucanase (PDB id: 3VDH); (i) Ruminiclostridium thermocellum multifunctional GH5 cellulase, xylanase and mannase (PDB id: 4IM4); (j) Bacteroidetes bacterium AC2a endocellulase (PDB id: 4YHE).	FIG
+212	225	endoglucanase	protein_type	(a) BlCel5B in the crystallographic and closed configuration; (b) Bacillus halodurans Cel5B (BhCel5B) (PDB id: 4V2X) (c) Piromyces rhizinflata GH5 endoglucanase (PDB id: 3AYR); (d) Clostridium cellulolyticum GH5 endoglucanase (PDB id: 1EDG); (e) Clostridium cellulovorans GH5 endoglucanase (PDB id: 3NDY); (f) Bacteroides ovatus GH5 xyloglucanase (PDB id: 3ZMR); (g) Paenibacillus pabuli GH5 xyloglucanase (PDB id: 2JEP); (h) Prevotella bryantii GH5 endoglucanase (PDB id: 3VDH); (i) Ruminiclostridium thermocellum multifunctional GH5 cellulase, xylanase and mannase (PDB id: 4IM4); (j) Bacteroidetes bacterium AC2a endocellulase (PDB id: 4YHE).	FIG
+246	271	Clostridium cellulovorans	species	(a) BlCel5B in the crystallographic and closed configuration; (b) Bacillus halodurans Cel5B (BhCel5B) (PDB id: 4V2X) (c) Piromyces rhizinflata GH5 endoglucanase (PDB id: 3AYR); (d) Clostridium cellulolyticum GH5 endoglucanase (PDB id: 1EDG); (e) Clostridium cellulovorans GH5 endoglucanase (PDB id: 3NDY); (f) Bacteroides ovatus GH5 xyloglucanase (PDB id: 3ZMR); (g) Paenibacillus pabuli GH5 xyloglucanase (PDB id: 2JEP); (h) Prevotella bryantii GH5 endoglucanase (PDB id: 3VDH); (i) Ruminiclostridium thermocellum multifunctional GH5 cellulase, xylanase and mannase (PDB id: 4IM4); (j) Bacteroidetes bacterium AC2a endocellulase (PDB id: 4YHE).	FIG
+272	275	GH5	protein_type	(a) BlCel5B in the crystallographic and closed configuration; (b) Bacillus halodurans Cel5B (BhCel5B) (PDB id: 4V2X) (c) Piromyces rhizinflata GH5 endoglucanase (PDB id: 3AYR); (d) Clostridium cellulolyticum GH5 endoglucanase (PDB id: 1EDG); (e) Clostridium cellulovorans GH5 endoglucanase (PDB id: 3NDY); (f) Bacteroides ovatus GH5 xyloglucanase (PDB id: 3ZMR); (g) Paenibacillus pabuli GH5 xyloglucanase (PDB id: 2JEP); (h) Prevotella bryantii GH5 endoglucanase (PDB id: 3VDH); (i) Ruminiclostridium thermocellum multifunctional GH5 cellulase, xylanase and mannase (PDB id: 4IM4); (j) Bacteroidetes bacterium AC2a endocellulase (PDB id: 4YHE).	FIG
+276	289	endoglucanase	protein_type	(a) BlCel5B in the crystallographic and closed configuration; (b) Bacillus halodurans Cel5B (BhCel5B) (PDB id: 4V2X) (c) Piromyces rhizinflata GH5 endoglucanase (PDB id: 3AYR); (d) Clostridium cellulolyticum GH5 endoglucanase (PDB id: 1EDG); (e) Clostridium cellulovorans GH5 endoglucanase (PDB id: 3NDY); (f) Bacteroides ovatus GH5 xyloglucanase (PDB id: 3ZMR); (g) Paenibacillus pabuli GH5 xyloglucanase (PDB id: 2JEP); (h) Prevotella bryantii GH5 endoglucanase (PDB id: 3VDH); (i) Ruminiclostridium thermocellum multifunctional GH5 cellulase, xylanase and mannase (PDB id: 4IM4); (j) Bacteroidetes bacterium AC2a endocellulase (PDB id: 4YHE).	FIG
+310	328	Bacteroides ovatus	species	(a) BlCel5B in the crystallographic and closed configuration; (b) Bacillus halodurans Cel5B (BhCel5B) (PDB id: 4V2X) (c) Piromyces rhizinflata GH5 endoglucanase (PDB id: 3AYR); (d) Clostridium cellulolyticum GH5 endoglucanase (PDB id: 1EDG); (e) Clostridium cellulovorans GH5 endoglucanase (PDB id: 3NDY); (f) Bacteroides ovatus GH5 xyloglucanase (PDB id: 3ZMR); (g) Paenibacillus pabuli GH5 xyloglucanase (PDB id: 2JEP); (h) Prevotella bryantii GH5 endoglucanase (PDB id: 3VDH); (i) Ruminiclostridium thermocellum multifunctional GH5 cellulase, xylanase and mannase (PDB id: 4IM4); (j) Bacteroidetes bacterium AC2a endocellulase (PDB id: 4YHE).	FIG
+329	332	GH5	protein_type	(a) BlCel5B in the crystallographic and closed configuration; (b) Bacillus halodurans Cel5B (BhCel5B) (PDB id: 4V2X) (c) Piromyces rhizinflata GH5 endoglucanase (PDB id: 3AYR); (d) Clostridium cellulolyticum GH5 endoglucanase (PDB id: 1EDG); (e) Clostridium cellulovorans GH5 endoglucanase (PDB id: 3NDY); (f) Bacteroides ovatus GH5 xyloglucanase (PDB id: 3ZMR); (g) Paenibacillus pabuli GH5 xyloglucanase (PDB id: 2JEP); (h) Prevotella bryantii GH5 endoglucanase (PDB id: 3VDH); (i) Ruminiclostridium thermocellum multifunctional GH5 cellulase, xylanase and mannase (PDB id: 4IM4); (j) Bacteroidetes bacterium AC2a endocellulase (PDB id: 4YHE).	FIG
+333	346	xyloglucanase	protein_type	(a) BlCel5B in the crystallographic and closed configuration; (b) Bacillus halodurans Cel5B (BhCel5B) (PDB id: 4V2X) (c) Piromyces rhizinflata GH5 endoglucanase (PDB id: 3AYR); (d) Clostridium cellulolyticum GH5 endoglucanase (PDB id: 1EDG); (e) Clostridium cellulovorans GH5 endoglucanase (PDB id: 3NDY); (f) Bacteroides ovatus GH5 xyloglucanase (PDB id: 3ZMR); (g) Paenibacillus pabuli GH5 xyloglucanase (PDB id: 2JEP); (h) Prevotella bryantii GH5 endoglucanase (PDB id: 3VDH); (i) Ruminiclostridium thermocellum multifunctional GH5 cellulase, xylanase and mannase (PDB id: 4IM4); (j) Bacteroidetes bacterium AC2a endocellulase (PDB id: 4YHE).	FIG
+367	387	Paenibacillus pabuli	species	(a) BlCel5B in the crystallographic and closed configuration; (b) Bacillus halodurans Cel5B (BhCel5B) (PDB id: 4V2X) (c) Piromyces rhizinflata GH5 endoglucanase (PDB id: 3AYR); (d) Clostridium cellulolyticum GH5 endoglucanase (PDB id: 1EDG); (e) Clostridium cellulovorans GH5 endoglucanase (PDB id: 3NDY); (f) Bacteroides ovatus GH5 xyloglucanase (PDB id: 3ZMR); (g) Paenibacillus pabuli GH5 xyloglucanase (PDB id: 2JEP); (h) Prevotella bryantii GH5 endoglucanase (PDB id: 3VDH); (i) Ruminiclostridium thermocellum multifunctional GH5 cellulase, xylanase and mannase (PDB id: 4IM4); (j) Bacteroidetes bacterium AC2a endocellulase (PDB id: 4YHE).	FIG
+388	391	GH5	protein_type	(a) BlCel5B in the crystallographic and closed configuration; (b) Bacillus halodurans Cel5B (BhCel5B) (PDB id: 4V2X) (c) Piromyces rhizinflata GH5 endoglucanase (PDB id: 3AYR); (d) Clostridium cellulolyticum GH5 endoglucanase (PDB id: 1EDG); (e) Clostridium cellulovorans GH5 endoglucanase (PDB id: 3NDY); (f) Bacteroides ovatus GH5 xyloglucanase (PDB id: 3ZMR); (g) Paenibacillus pabuli GH5 xyloglucanase (PDB id: 2JEP); (h) Prevotella bryantii GH5 endoglucanase (PDB id: 3VDH); (i) Ruminiclostridium thermocellum multifunctional GH5 cellulase, xylanase and mannase (PDB id: 4IM4); (j) Bacteroidetes bacterium AC2a endocellulase (PDB id: 4YHE).	FIG
+392	405	xyloglucanase	protein_type	(a) BlCel5B in the crystallographic and closed configuration; (b) Bacillus halodurans Cel5B (BhCel5B) (PDB id: 4V2X) (c) Piromyces rhizinflata GH5 endoglucanase (PDB id: 3AYR); (d) Clostridium cellulolyticum GH5 endoglucanase (PDB id: 1EDG); (e) Clostridium cellulovorans GH5 endoglucanase (PDB id: 3NDY); (f) Bacteroides ovatus GH5 xyloglucanase (PDB id: 3ZMR); (g) Paenibacillus pabuli GH5 xyloglucanase (PDB id: 2JEP); (h) Prevotella bryantii GH5 endoglucanase (PDB id: 3VDH); (i) Ruminiclostridium thermocellum multifunctional GH5 cellulase, xylanase and mannase (PDB id: 4IM4); (j) Bacteroidetes bacterium AC2a endocellulase (PDB id: 4YHE).	FIG
+426	445	Prevotella bryantii	species	(a) BlCel5B in the crystallographic and closed configuration; (b) Bacillus halodurans Cel5B (BhCel5B) (PDB id: 4V2X) (c) Piromyces rhizinflata GH5 endoglucanase (PDB id: 3AYR); (d) Clostridium cellulolyticum GH5 endoglucanase (PDB id: 1EDG); (e) Clostridium cellulovorans GH5 endoglucanase (PDB id: 3NDY); (f) Bacteroides ovatus GH5 xyloglucanase (PDB id: 3ZMR); (g) Paenibacillus pabuli GH5 xyloglucanase (PDB id: 2JEP); (h) Prevotella bryantii GH5 endoglucanase (PDB id: 3VDH); (i) Ruminiclostridium thermocellum multifunctional GH5 cellulase, xylanase and mannase (PDB id: 4IM4); (j) Bacteroidetes bacterium AC2a endocellulase (PDB id: 4YHE).	FIG
+446	449	GH5	protein_type	(a) BlCel5B in the crystallographic and closed configuration; (b) Bacillus halodurans Cel5B (BhCel5B) (PDB id: 4V2X) (c) Piromyces rhizinflata GH5 endoglucanase (PDB id: 3AYR); (d) Clostridium cellulolyticum GH5 endoglucanase (PDB id: 1EDG); (e) Clostridium cellulovorans GH5 endoglucanase (PDB id: 3NDY); (f) Bacteroides ovatus GH5 xyloglucanase (PDB id: 3ZMR); (g) Paenibacillus pabuli GH5 xyloglucanase (PDB id: 2JEP); (h) Prevotella bryantii GH5 endoglucanase (PDB id: 3VDH); (i) Ruminiclostridium thermocellum multifunctional GH5 cellulase, xylanase and mannase (PDB id: 4IM4); (j) Bacteroidetes bacterium AC2a endocellulase (PDB id: 4YHE).	FIG
+450	463	endoglucanase	protein_type	(a) BlCel5B in the crystallographic and closed configuration; (b) Bacillus halodurans Cel5B (BhCel5B) (PDB id: 4V2X) (c) Piromyces rhizinflata GH5 endoglucanase (PDB id: 3AYR); (d) Clostridium cellulolyticum GH5 endoglucanase (PDB id: 1EDG); (e) Clostridium cellulovorans GH5 endoglucanase (PDB id: 3NDY); (f) Bacteroides ovatus GH5 xyloglucanase (PDB id: 3ZMR); (g) Paenibacillus pabuli GH5 xyloglucanase (PDB id: 2JEP); (h) Prevotella bryantii GH5 endoglucanase (PDB id: 3VDH); (i) Ruminiclostridium thermocellum multifunctional GH5 cellulase, xylanase and mannase (PDB id: 4IM4); (j) Bacteroidetes bacterium AC2a endocellulase (PDB id: 4YHE).	FIG
+484	514	Ruminiclostridium thermocellum	species	(a) BlCel5B in the crystallographic and closed configuration; (b) Bacillus halodurans Cel5B (BhCel5B) (PDB id: 4V2X) (c) Piromyces rhizinflata GH5 endoglucanase (PDB id: 3AYR); (d) Clostridium cellulolyticum GH5 endoglucanase (PDB id: 1EDG); (e) Clostridium cellulovorans GH5 endoglucanase (PDB id: 3NDY); (f) Bacteroides ovatus GH5 xyloglucanase (PDB id: 3ZMR); (g) Paenibacillus pabuli GH5 xyloglucanase (PDB id: 2JEP); (h) Prevotella bryantii GH5 endoglucanase (PDB id: 3VDH); (i) Ruminiclostridium thermocellum multifunctional GH5 cellulase, xylanase and mannase (PDB id: 4IM4); (j) Bacteroidetes bacterium AC2a endocellulase (PDB id: 4YHE).	FIG
+531	534	GH5	protein_type	(a) BlCel5B in the crystallographic and closed configuration; (b) Bacillus halodurans Cel5B (BhCel5B) (PDB id: 4V2X) (c) Piromyces rhizinflata GH5 endoglucanase (PDB id: 3AYR); (d) Clostridium cellulolyticum GH5 endoglucanase (PDB id: 1EDG); (e) Clostridium cellulovorans GH5 endoglucanase (PDB id: 3NDY); (f) Bacteroides ovatus GH5 xyloglucanase (PDB id: 3ZMR); (g) Paenibacillus pabuli GH5 xyloglucanase (PDB id: 2JEP); (h) Prevotella bryantii GH5 endoglucanase (PDB id: 3VDH); (i) Ruminiclostridium thermocellum multifunctional GH5 cellulase, xylanase and mannase (PDB id: 4IM4); (j) Bacteroidetes bacterium AC2a endocellulase (PDB id: 4YHE).	FIG
+535	544	cellulase	protein_type	(a) BlCel5B in the crystallographic and closed configuration; (b) Bacillus halodurans Cel5B (BhCel5B) (PDB id: 4V2X) (c) Piromyces rhizinflata GH5 endoglucanase (PDB id: 3AYR); (d) Clostridium cellulolyticum GH5 endoglucanase (PDB id: 1EDG); (e) Clostridium cellulovorans GH5 endoglucanase (PDB id: 3NDY); (f) Bacteroides ovatus GH5 xyloglucanase (PDB id: 3ZMR); (g) Paenibacillus pabuli GH5 xyloglucanase (PDB id: 2JEP); (h) Prevotella bryantii GH5 endoglucanase (PDB id: 3VDH); (i) Ruminiclostridium thermocellum multifunctional GH5 cellulase, xylanase and mannase (PDB id: 4IM4); (j) Bacteroidetes bacterium AC2a endocellulase (PDB id: 4YHE).	FIG
+546	554	xylanase	protein_type	(a) BlCel5B in the crystallographic and closed configuration; (b) Bacillus halodurans Cel5B (BhCel5B) (PDB id: 4V2X) (c) Piromyces rhizinflata GH5 endoglucanase (PDB id: 3AYR); (d) Clostridium cellulolyticum GH5 endoglucanase (PDB id: 1EDG); (e) Clostridium cellulovorans GH5 endoglucanase (PDB id: 3NDY); (f) Bacteroides ovatus GH5 xyloglucanase (PDB id: 3ZMR); (g) Paenibacillus pabuli GH5 xyloglucanase (PDB id: 2JEP); (h) Prevotella bryantii GH5 endoglucanase (PDB id: 3VDH); (i) Ruminiclostridium thermocellum multifunctional GH5 cellulase, xylanase and mannase (PDB id: 4IM4); (j) Bacteroidetes bacterium AC2a endocellulase (PDB id: 4YHE).	FIG
+559	566	mannase	protein_type	(a) BlCel5B in the crystallographic and closed configuration; (b) Bacillus halodurans Cel5B (BhCel5B) (PDB id: 4V2X) (c) Piromyces rhizinflata GH5 endoglucanase (PDB id: 3AYR); (d) Clostridium cellulolyticum GH5 endoglucanase (PDB id: 1EDG); (e) Clostridium cellulovorans GH5 endoglucanase (PDB id: 3NDY); (f) Bacteroides ovatus GH5 xyloglucanase (PDB id: 3ZMR); (g) Paenibacillus pabuli GH5 xyloglucanase (PDB id: 2JEP); (h) Prevotella bryantii GH5 endoglucanase (PDB id: 3VDH); (i) Ruminiclostridium thermocellum multifunctional GH5 cellulase, xylanase and mannase (PDB id: 4IM4); (j) Bacteroidetes bacterium AC2a endocellulase (PDB id: 4YHE).	FIG
+587	610	Bacteroidetes bacterium	taxonomy_domain	(a) BlCel5B in the crystallographic and closed configuration; (b) Bacillus halodurans Cel5B (BhCel5B) (PDB id: 4V2X) (c) Piromyces rhizinflata GH5 endoglucanase (PDB id: 3AYR); (d) Clostridium cellulolyticum GH5 endoglucanase (PDB id: 1EDG); (e) Clostridium cellulovorans GH5 endoglucanase (PDB id: 3NDY); (f) Bacteroides ovatus GH5 xyloglucanase (PDB id: 3ZMR); (g) Paenibacillus pabuli GH5 xyloglucanase (PDB id: 2JEP); (h) Prevotella bryantii GH5 endoglucanase (PDB id: 3VDH); (i) Ruminiclostridium thermocellum multifunctional GH5 cellulase, xylanase and mannase (PDB id: 4IM4); (j) Bacteroidetes bacterium AC2a endocellulase (PDB id: 4YHE).	FIG
+611	615	AC2a	protein_type	(a) BlCel5B in the crystallographic and closed configuration; (b) Bacillus halodurans Cel5B (BhCel5B) (PDB id: 4V2X) (c) Piromyces rhizinflata GH5 endoglucanase (PDB id: 3AYR); (d) Clostridium cellulolyticum GH5 endoglucanase (PDB id: 1EDG); (e) Clostridium cellulovorans GH5 endoglucanase (PDB id: 3NDY); (f) Bacteroides ovatus GH5 xyloglucanase (PDB id: 3ZMR); (g) Paenibacillus pabuli GH5 xyloglucanase (PDB id: 2JEP); (h) Prevotella bryantii GH5 endoglucanase (PDB id: 3VDH); (i) Ruminiclostridium thermocellum multifunctional GH5 cellulase, xylanase and mannase (PDB id: 4IM4); (j) Bacteroidetes bacterium AC2a endocellulase (PDB id: 4YHE).	FIG
+616	629	endocellulase	protein_type	(a) BlCel5B in the crystallographic and closed configuration; (b) Bacillus halodurans Cel5B (BhCel5B) (PDB id: 4V2X) (c) Piromyces rhizinflata GH5 endoglucanase (PDB id: 3AYR); (d) Clostridium cellulolyticum GH5 endoglucanase (PDB id: 1EDG); (e) Clostridium cellulovorans GH5 endoglucanase (PDB id: 3NDY); (f) Bacteroides ovatus GH5 xyloglucanase (PDB id: 3ZMR); (g) Paenibacillus pabuli GH5 xyloglucanase (PDB id: 2JEP); (h) Prevotella bryantii GH5 endoglucanase (PDB id: 3VDH); (i) Ruminiclostridium thermocellum multifunctional GH5 cellulase, xylanase and mannase (PDB id: 4IM4); (j) Bacteroidetes bacterium AC2a endocellulase (PDB id: 4YHE).	FIG
+0	10	Comparison	experimental_method	Comparison of the binding cleft of the BlCel5B and BhCel5B.	FIG
+18	31	binding cleft	site	Comparison of the binding cleft of the BlCel5B and BhCel5B.	FIG
+39	46	BlCel5B	protein	Comparison of the binding cleft of the BlCel5B and BhCel5B.	FIG
+51	58	BhCel5B	protein	Comparison of the binding cleft of the BlCel5B and BhCel5B.	FIG
+28	35	BlCel5B	protein	The main difference between BlCel5B and BhCel5B is that the latter exhibits a deeper cleft due to the presence of residue W181 in the loop between F177 and R185.	FIG
+40	47	BhCel5B	protein	The main difference between BlCel5B and BhCel5B is that the latter exhibits a deeper cleft due to the presence of residue W181 in the loop between F177 and R185.	FIG
+85	90	cleft	site	The main difference between BlCel5B and BhCel5B is that the latter exhibits a deeper cleft due to the presence of residue W181 in the loop between F177 and R185.	FIG
+102	113	presence of	protein_state	The main difference between BlCel5B and BhCel5B is that the latter exhibits a deeper cleft due to the presence of residue W181 in the loop between F177 and R185.	FIG
+122	126	W181	residue_name_number	The main difference between BlCel5B and BhCel5B is that the latter exhibits a deeper cleft due to the presence of residue W181 in the loop between F177 and R185.	FIG
+134	138	loop	structure_element	The main difference between BlCel5B and BhCel5B is that the latter exhibits a deeper cleft due to the presence of residue W181 in the loop between F177 and R185.	FIG
+147	151	F177	residue_name_number	The main difference between BlCel5B and BhCel5B is that the latter exhibits a deeper cleft due to the presence of residue W181 in the loop between F177 and R185.	FIG
+156	160	R185	residue_name_number	The main difference between BlCel5B and BhCel5B is that the latter exhibits a deeper cleft due to the presence of residue W181 in the loop between F177 and R185.	FIG
+42	54	binding site	site	We conjecture that this difference in the binding site architecture relates to the importance that the CBM46 plays in the BlCel5B enzymatic mechanism.	FIG
+103	108	CBM46	structure_element	We conjecture that this difference in the binding site architecture relates to the importance that the CBM46 plays in the BlCel5B enzymatic mechanism.	FIG
+122	129	BlCel5B	protein	We conjecture that this difference in the binding site architecture relates to the importance that the CBM46 plays in the BlCel5B enzymatic mechanism.	FIG
+32	39	BlCel5B	protein	Proposed molecular mechanism of BlCel5B conformational selection.	FIG
+20	31	simulations	experimental_method	As suggested by the simulations and SAXS data, BlCel5B spans multiple conformations ranging from closed to extended CBM46/CD states.	FIG
+36	40	SAXS	experimental_method	As suggested by the simulations and SAXS data, BlCel5B spans multiple conformations ranging from closed to extended CBM46/CD states.	FIG
+47	54	BlCel5B	protein	As suggested by the simulations and SAXS data, BlCel5B spans multiple conformations ranging from closed to extended CBM46/CD states.	FIG
+97	103	closed	protein_state	As suggested by the simulations and SAXS data, BlCel5B spans multiple conformations ranging from closed to extended CBM46/CD states.	FIG
+107	115	extended	protein_state	As suggested by the simulations and SAXS data, BlCel5B spans multiple conformations ranging from closed to extended CBM46/CD states.	FIG
+116	121	CBM46	structure_element	As suggested by the simulations and SAXS data, BlCel5B spans multiple conformations ranging from closed to extended CBM46/CD states.	FIG
+122	124	CD	structure_element	As suggested by the simulations and SAXS data, BlCel5B spans multiple conformations ranging from closed to extended CBM46/CD states.	FIG
+11	15	open	protein_state	In a given open state, the substrate may reach the active site and become entrapped by the capping of CBM46 onto CD and induced-fit conformational adjustments.	FIG
+51	62	active site	site	In a given open state, the substrate may reach the active site and become entrapped by the capping of CBM46 onto CD and induced-fit conformational adjustments.	FIG
+102	107	CBM46	structure_element	In a given open state, the substrate may reach the active site and become entrapped by the capping of CBM46 onto CD and induced-fit conformational adjustments.	FIG
+113	115	CD	structure_element	In a given open state, the substrate may reach the active site and become entrapped by the capping of CBM46 onto CD and induced-fit conformational adjustments.	FIG
+60	63	apo	protein_state	After hydrolysis, the reaction product is released to yield apo-BlCel5B, which becomes ready for a new cycle.	FIG
+64	71	BlCel5B	protein	After hydrolysis, the reaction product is released to yield apo-BlCel5B, which becomes ready for a new cycle.	FIG
+12	19	BlCel5B	protein	Activity of BlCel5B constructs against tested substrates.	TABLE
+39	41	WT	protein_state	"Substrate (1%)	Relative Activity (%)	 	WT*	W479A	W481A	ΔCBM46	ΔIg-CBM46	 	β-glucan	100	79.1	63.6	nd	nd	 	CMC	25.5	12.2	2.4	nd	nd	 	Lichenan	52.4	41	28.6	nd	nd	 	Xyloglucan	45.2	41.2	30.8	nd	nd	 	Azo-Avicel	nd**	nd	nd	nd	nd	 	Arabinoxylan	nd	nd	nd	nd	nd	 	Galactomannan	nd	nd	nd	nd	nd	 	1,4-β-mannan	nd	nd	nd	nd	nd	 	"	TABLE
+43	48	W479A	mutant	"Substrate (1%)	Relative Activity (%)	 	WT*	W479A	W481A	ΔCBM46	ΔIg-CBM46	 	β-glucan	100	79.1	63.6	nd	nd	 	CMC	25.5	12.2	2.4	nd	nd	 	Lichenan	52.4	41	28.6	nd	nd	 	Xyloglucan	45.2	41.2	30.8	nd	nd	 	Azo-Avicel	nd**	nd	nd	nd	nd	 	Arabinoxylan	nd	nd	nd	nd	nd	 	Galactomannan	nd	nd	nd	nd	nd	 	1,4-β-mannan	nd	nd	nd	nd	nd	 	"	TABLE
+49	54	W481A	mutant	"Substrate (1%)	Relative Activity (%)	 	WT*	W479A	W481A	ΔCBM46	ΔIg-CBM46	 	β-glucan	100	79.1	63.6	nd	nd	 	CMC	25.5	12.2	2.4	nd	nd	 	Lichenan	52.4	41	28.6	nd	nd	 	Xyloglucan	45.2	41.2	30.8	nd	nd	 	Azo-Avicel	nd**	nd	nd	nd	nd	 	Arabinoxylan	nd	nd	nd	nd	nd	 	Galactomannan	nd	nd	nd	nd	nd	 	1,4-β-mannan	nd	nd	nd	nd	nd	 	"	TABLE
+55	61	ΔCBM46	mutant	"Substrate (1%)	Relative Activity (%)	 	WT*	W479A	W481A	ΔCBM46	ΔIg-CBM46	 	β-glucan	100	79.1	63.6	nd	nd	 	CMC	25.5	12.2	2.4	nd	nd	 	Lichenan	52.4	41	28.6	nd	nd	 	Xyloglucan	45.2	41.2	30.8	nd	nd	 	Azo-Avicel	nd**	nd	nd	nd	nd	 	Arabinoxylan	nd	nd	nd	nd	nd	 	Galactomannan	nd	nd	nd	nd	nd	 	1,4-β-mannan	nd	nd	nd	nd	nd	 	"	TABLE
+62	71	ΔIg-CBM46	mutant	"Substrate (1%)	Relative Activity (%)	 	WT*	W479A	W481A	ΔCBM46	ΔIg-CBM46	 	β-glucan	100	79.1	63.6	nd	nd	 	CMC	25.5	12.2	2.4	nd	nd	 	Lichenan	52.4	41	28.6	nd	nd	 	Xyloglucan	45.2	41.2	30.8	nd	nd	 	Azo-Avicel	nd**	nd	nd	nd	nd	 	Arabinoxylan	nd	nd	nd	nd	nd	 	Galactomannan	nd	nd	nd	nd	nd	 	1,4-β-mannan	nd	nd	nd	nd	nd	 	"	TABLE
+74	82	β-glucan	chemical	"Substrate (1%)	Relative Activity (%)	 	WT*	W479A	W481A	ΔCBM46	ΔIg-CBM46	 	β-glucan	100	79.1	63.6	nd	nd	 	CMC	25.5	12.2	2.4	nd	nd	 	Lichenan	52.4	41	28.6	nd	nd	 	Xyloglucan	45.2	41.2	30.8	nd	nd	 	Azo-Avicel	nd**	nd	nd	nd	nd	 	Arabinoxylan	nd	nd	nd	nd	nd	 	Galactomannan	nd	nd	nd	nd	nd	 	1,4-β-mannan	nd	nd	nd	nd	nd	 	"	TABLE
+105	108	CMC	chemical	"Substrate (1%)	Relative Activity (%)	 	WT*	W479A	W481A	ΔCBM46	ΔIg-CBM46	 	β-glucan	100	79.1	63.6	nd	nd	 	CMC	25.5	12.2	2.4	nd	nd	 	Lichenan	52.4	41	28.6	nd	nd	 	Xyloglucan	45.2	41.2	30.8	nd	nd	 	Azo-Avicel	nd**	nd	nd	nd	nd	 	Arabinoxylan	nd	nd	nd	nd	nd	 	Galactomannan	nd	nd	nd	nd	nd	 	1,4-β-mannan	nd	nd	nd	nd	nd	 	"	TABLE
+131	139	Lichenan	chemical	"Substrate (1%)	Relative Activity (%)	 	WT*	W479A	W481A	ΔCBM46	ΔIg-CBM46	 	β-glucan	100	79.1	63.6	nd	nd	 	CMC	25.5	12.2	2.4	nd	nd	 	Lichenan	52.4	41	28.6	nd	nd	 	Xyloglucan	45.2	41.2	30.8	nd	nd	 	Azo-Avicel	nd**	nd	nd	nd	nd	 	Arabinoxylan	nd	nd	nd	nd	nd	 	Galactomannan	nd	nd	nd	nd	nd	 	1,4-β-mannan	nd	nd	nd	nd	nd	 	"	TABLE
+161	171	Xyloglucan	chemical	"Substrate (1%)	Relative Activity (%)	 	WT*	W479A	W481A	ΔCBM46	ΔIg-CBM46	 	β-glucan	100	79.1	63.6	nd	nd	 	CMC	25.5	12.2	2.4	nd	nd	 	Lichenan	52.4	41	28.6	nd	nd	 	Xyloglucan	45.2	41.2	30.8	nd	nd	 	Azo-Avicel	nd**	nd	nd	nd	nd	 	Arabinoxylan	nd	nd	nd	nd	nd	 	Galactomannan	nd	nd	nd	nd	nd	 	1,4-β-mannan	nd	nd	nd	nd	nd	 	"	TABLE
+195	205	Azo-Avicel	chemical	"Substrate (1%)	Relative Activity (%)	 	WT*	W479A	W481A	ΔCBM46	ΔIg-CBM46	 	β-glucan	100	79.1	63.6	nd	nd	 	CMC	25.5	12.2	2.4	nd	nd	 	Lichenan	52.4	41	28.6	nd	nd	 	Xyloglucan	45.2	41.2	30.8	nd	nd	 	Azo-Avicel	nd**	nd	nd	nd	nd	 	Arabinoxylan	nd	nd	nd	nd	nd	 	Galactomannan	nd	nd	nd	nd	nd	 	1,4-β-mannan	nd	nd	nd	nd	nd	 	"	TABLE
+225	237	Arabinoxylan	chemical	"Substrate (1%)	Relative Activity (%)	 	WT*	W479A	W481A	ΔCBM46	ΔIg-CBM46	 	β-glucan	100	79.1	63.6	nd	nd	 	CMC	25.5	12.2	2.4	nd	nd	 	Lichenan	52.4	41	28.6	nd	nd	 	Xyloglucan	45.2	41.2	30.8	nd	nd	 	Azo-Avicel	nd**	nd	nd	nd	nd	 	Arabinoxylan	nd	nd	nd	nd	nd	 	Galactomannan	nd	nd	nd	nd	nd	 	1,4-β-mannan	nd	nd	nd	nd	nd	 	"	TABLE
+255	268	Galactomannan	chemical	"Substrate (1%)	Relative Activity (%)	 	WT*	W479A	W481A	ΔCBM46	ΔIg-CBM46	 	β-glucan	100	79.1	63.6	nd	nd	 	CMC	25.5	12.2	2.4	nd	nd	 	Lichenan	52.4	41	28.6	nd	nd	 	Xyloglucan	45.2	41.2	30.8	nd	nd	 	Azo-Avicel	nd**	nd	nd	nd	nd	 	Arabinoxylan	nd	nd	nd	nd	nd	 	Galactomannan	nd	nd	nd	nd	nd	 	1,4-β-mannan	nd	nd	nd	nd	nd	 	"	TABLE
+286	298	1,4-β-mannan	chemical	"Substrate (1%)	Relative Activity (%)	 	WT*	W479A	W481A	ΔCBM46	ΔIg-CBM46	 	β-glucan	100	79.1	63.6	nd	nd	 	CMC	25.5	12.2	2.4	nd	nd	 	Lichenan	52.4	41	28.6	nd	nd	 	Xyloglucan	45.2	41.2	30.8	nd	nd	 	Azo-Avicel	nd**	nd	nd	nd	nd	 	Arabinoxylan	nd	nd	nd	nd	nd	 	Galactomannan	nd	nd	nd	nd	nd	 	1,4-β-mannan	nd	nd	nd	nd	nd	 	"	TABLE
+1	3	WT	protein_state	*WT = wild type.	TABLE
+6	15	wild type	protein_state	*WT = wild type.	TABLE