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6 13 Cryo-EM experimental_method Using Cryo-EM to Map Small Ligands on Dynamic Metabolic Enzymes: Studies with Glutamate Dehydrogenase TITLE
78 101 Glutamate Dehydrogenase protein_type Using Cryo-EM to Map Small Ligands on Dynamic Metabolic Enzymes: Studies with Glutamate Dehydrogenase TITLE
0 24 Cryo-electron microscopy experimental_method Cryo-electron microscopy (cryo-EM) methods are now being used to determine structures at near-atomic resolution and have great promise in molecular pharmacology, especially in the context of mapping the binding of small-molecule ligands to protein complexes that display conformational flexibility. ABSTRACT
26 33 cryo-EM experimental_method Cryo-electron microscopy (cryo-EM) methods are now being used to determine structures at near-atomic resolution and have great promise in molecular pharmacology, especially in the context of mapping the binding of small-molecule ligands to protein complexes that display conformational flexibility. ABSTRACT
75 85 structures evidence Cryo-electron microscopy (cryo-EM) methods are now being used to determine structures at near-atomic resolution and have great promise in molecular pharmacology, especially in the context of mapping the binding of small-molecule ligands to protein complexes that display conformational flexibility. ABSTRACT
30 53 glutamate dehydrogenase protein_type We illustrate this here using glutamate dehydrogenase (GDH), a 336-kDa metabolic enzyme that catalyzes the oxidative deamination of glutamate. ABSTRACT
55 58 GDH protein_type We illustrate this here using glutamate dehydrogenase (GDH), a 336-kDa metabolic enzyme that catalyzes the oxidative deamination of glutamate. ABSTRACT
132 141 glutamate chemical We illustrate this here using glutamate dehydrogenase (GDH), a 336-kDa metabolic enzyme that catalyzes the oxidative deamination of glutamate. ABSTRACT
17 20 GDH protein_type Dysregulation of GDH leads to a variety of metabolic and neurologic disorders. ABSTRACT
39 46 cryo-EM experimental_method Here, we report near-atomic resolution cryo-EM structures, at resolutions ranging from 3.2 Å to 3.6 Å for GDH complexes, including complexes for which crystal structures are not available. ABSTRACT
47 57 structures evidence Here, we report near-atomic resolution cryo-EM structures, at resolutions ranging from 3.2 Å to 3.6 Å for GDH complexes, including complexes for which crystal structures are not available. ABSTRACT
106 109 GDH protein_type Here, we report near-atomic resolution cryo-EM structures, at resolutions ranging from 3.2 Å to 3.6 Å for GDH complexes, including complexes for which crystal structures are not available. ABSTRACT
151 169 crystal structures evidence Here, we report near-atomic resolution cryo-EM structures, at resolutions ranging from 3.2 Å to 3.6 Å for GDH complexes, including complexes for which crystal structures are not available. ABSTRACT
41 45 NADH chemical We show that the binding of the coenzyme NADH alone or in concert with GTP results in a binary mixture in which the enzyme is in either an “open” or “closed” state. ABSTRACT
71 74 GTP chemical We show that the binding of the coenzyme NADH alone or in concert with GTP results in a binary mixture in which the enzyme is in either an “open” or “closed” state. ABSTRACT
140 144 open protein_state We show that the binding of the coenzyme NADH alone or in concert with GTP results in a binary mixture in which the enzyme is in either an “open” or “closed” state. ABSTRACT
150 156 closed protein_state We show that the binding of the coenzyme NADH alone or in concert with GTP results in a binary mixture in which the enzyme is in either an “open” or “closed” state. ABSTRACT
12 21 structure evidence Whereas the structure of NADH in the active site is similar between the open and closed states, it is unexpectedly different at the regulatory site. ABSTRACT
25 29 NADH chemical Whereas the structure of NADH in the active site is similar between the open and closed states, it is unexpectedly different at the regulatory site. ABSTRACT
37 48 active site site Whereas the structure of NADH in the active site is similar between the open and closed states, it is unexpectedly different at the regulatory site. ABSTRACT
72 76 open protein_state Whereas the structure of NADH in the active site is similar between the open and closed states, it is unexpectedly different at the regulatory site. ABSTRACT
81 87 closed protein_state Whereas the structure of NADH in the active site is similar between the open and closed states, it is unexpectedly different at the regulatory site. ABSTRACT
132 147 regulatory site site Whereas the structure of NADH in the active site is similar between the open and closed states, it is unexpectedly different at the regulatory site. ABSTRACT
117 138 X-ray crystallography experimental_method Our studies thus demonstrate that even in instances when there is considerable structural information available from X-ray crystallography, cryo-EM methods can provide useful complementary insights into regulatory mechanisms for dynamic protein complexes. ABSTRACT
140 147 cryo-EM experimental_method Our studies thus demonstrate that even in instances when there is considerable structural information available from X-ray crystallography, cryo-EM methods can provide useful complementary insights into regulatory mechanisms for dynamic protein complexes. ABSTRACT
19 43 cryo-electron microscopy experimental_method Recent advances in cryo-electron microscopy (cryo-EM) allow determination of structures of small protein complexes and membrane proteins at near-atomic resolution, marking a critical shift in the structural biology field. INTRO
45 52 cryo-EM experimental_method Recent advances in cryo-electron microscopy (cryo-EM) allow determination of structures of small protein complexes and membrane proteins at near-atomic resolution, marking a critical shift in the structural biology field. INTRO
77 87 structures evidence Recent advances in cryo-electron microscopy (cryo-EM) allow determination of structures of small protein complexes and membrane proteins at near-atomic resolution, marking a critical shift in the structural biology field. INTRO
150 165 crystallization experimental_method One specific area of broad general interest in drug discovery is the localization of bound ligands and cofactors under conditions in which efforts at crystallization have not been successful because of structural heterogeneity. INTRO
7 14 cryo-EM experimental_method Recent cryo-EM analyses have already demonstrated that it is now possible to use single-particle cryo-EM methods to localize small bound ligands or inhibitors on target proteins. INTRO
81 104 single-particle cryo-EM experimental_method Recent cryo-EM analyses have already demonstrated that it is now possible to use single-particle cryo-EM methods to localize small bound ligands or inhibitors on target proteins. INTRO
37 46 mammalian taxonomy_domain Here, we address this question using mammalian glutamate dehydrogenase as an example. INTRO
47 70 glutamate dehydrogenase protein_type Here, we address this question using mammalian glutamate dehydrogenase as an example. INTRO
0 23 Glutamate dehydrogenase protein_type Glutamate dehydrogenase (GDH) is a highly conserved enzyme expressed in most organisms. INTRO
25 28 GDH protein_type Glutamate dehydrogenase (GDH) is a highly conserved enzyme expressed in most organisms. INTRO
35 51 highly conserved protein_state Glutamate dehydrogenase (GDH) is a highly conserved enzyme expressed in most organisms. INTRO
0 3 GDH protein_type GDH plays a central role in glutamate metabolism by catalyzing the reversible oxidative deamination of glutamate to generate α-ketoglutarate and ammonia, with the concomitant transfer of a pair of electrons to either NAD+ or NADP+. INTRO
28 37 glutamate chemical GDH plays a central role in glutamate metabolism by catalyzing the reversible oxidative deamination of glutamate to generate α-ketoglutarate and ammonia, with the concomitant transfer of a pair of electrons to either NAD+ or NADP+. INTRO
103 112 glutamate chemical GDH plays a central role in glutamate metabolism by catalyzing the reversible oxidative deamination of glutamate to generate α-ketoglutarate and ammonia, with the concomitant transfer of a pair of electrons to either NAD+ or NADP+. INTRO
125 140 α-ketoglutarate chemical GDH plays a central role in glutamate metabolism by catalyzing the reversible oxidative deamination of glutamate to generate α-ketoglutarate and ammonia, with the concomitant transfer of a pair of electrons to either NAD+ or NADP+. INTRO
145 152 ammonia chemical GDH plays a central role in glutamate metabolism by catalyzing the reversible oxidative deamination of glutamate to generate α-ketoglutarate and ammonia, with the concomitant transfer of a pair of electrons to either NAD+ or NADP+. INTRO
217 221 NAD+ chemical GDH plays a central role in glutamate metabolism by catalyzing the reversible oxidative deamination of glutamate to generate α-ketoglutarate and ammonia, with the concomitant transfer of a pair of electrons to either NAD+ or NADP+. INTRO
225 230 NADP+ chemical GDH plays a central role in glutamate metabolism by catalyzing the reversible oxidative deamination of glutamate to generate α-ketoglutarate and ammonia, with the concomitant transfer of a pair of electrons to either NAD+ or NADP+. INTRO
14 17 GDH protein_type Regulation of GDH is tightly controlled through multiple allosteric mechanisms. INTRO
10 50 biochemical and crystallographic studies experimental_method Extensive biochemical and crystallographic studies have characterized the enzymatic activity of GDH and its modulation by a chemically diverse group of compounds such as nucleotides, amino acids, steroid hormones, antipsychotic drugs, and natural products. INTRO
96 99 GDH protein_type Extensive biochemical and crystallographic studies have characterized the enzymatic activity of GDH and its modulation by a chemically diverse group of compounds such as nucleotides, amino acids, steroid hormones, antipsychotic drugs, and natural products. INTRO
0 30 X-ray crystallographic studies experimental_method X-ray crystallographic studies have shown that the functional unit of GDH is a homohexamer composed of a trimer of dimers, with a 3-fold axis and an equatorial plane that define its D3 symmetry (Fig. 1A). INTRO
70 73 GDH protein_type X-ray crystallographic studies have shown that the functional unit of GDH is a homohexamer composed of a trimer of dimers, with a 3-fold axis and an equatorial plane that define its D3 symmetry (Fig. 1A). INTRO
79 90 homohexamer oligomeric_state X-ray crystallographic studies have shown that the functional unit of GDH is a homohexamer composed of a trimer of dimers, with a 3-fold axis and an equatorial plane that define its D3 symmetry (Fig. 1A). INTRO
105 111 trimer oligomeric_state X-ray crystallographic studies have shown that the functional unit of GDH is a homohexamer composed of a trimer of dimers, with a 3-fold axis and an equatorial plane that define its D3 symmetry (Fig. 1A). INTRO
115 121 dimers oligomeric_state X-ray crystallographic studies have shown that the functional unit of GDH is a homohexamer composed of a trimer of dimers, with a 3-fold axis and an equatorial plane that define its D3 symmetry (Fig. 1A). INTRO
12 20 protomer oligomeric_state Each 56-kDa protomer consists of three domains. INTRO
30 45 dimer interface site The first is located near the dimer interface and forms the core of the hexamer. INTRO
72 79 hexamer oligomeric_state The first is located near the dimer interface and forms the core of the hexamer. INTRO
14 39 nucleotide-binding domain structure_element The second, a nucleotide-binding domain (NBD) with a Rossmann fold, defines one face of the catalytic cleft bounded by the core domain. INTRO
41 44 NBD structure_element The second, a nucleotide-binding domain (NBD) with a Rossmann fold, defines one face of the catalytic cleft bounded by the core domain. INTRO
53 66 Rossmann fold structure_element The second, a nucleotide-binding domain (NBD) with a Rossmann fold, defines one face of the catalytic cleft bounded by the core domain. INTRO
92 107 catalytic cleft site The second, a nucleotide-binding domain (NBD) with a Rossmann fold, defines one face of the catalytic cleft bounded by the core domain. INTRO
32 35 NBD structure_element During the catalytic cycle, the NBD executes a large movement, hinged around a “pivot” helix, that closes the catalytic cleft, and drives a large conformational change in the hexamer from open to closed states (Fig. 1B). INTRO
79 92 “pivot” helix structure_element During the catalytic cycle, the NBD executes a large movement, hinged around a “pivot” helix, that closes the catalytic cleft, and drives a large conformational change in the hexamer from open to closed states (Fig. 1B). INTRO
110 125 catalytic cleft site During the catalytic cycle, the NBD executes a large movement, hinged around a “pivot” helix, that closes the catalytic cleft, and drives a large conformational change in the hexamer from open to closed states (Fig. 1B). INTRO
175 182 hexamer oligomeric_state During the catalytic cycle, the NBD executes a large movement, hinged around a “pivot” helix, that closes the catalytic cleft, and drives a large conformational change in the hexamer from open to closed states (Fig. 1B). INTRO
188 192 open protein_state During the catalytic cycle, the NBD executes a large movement, hinged around a “pivot” helix, that closes the catalytic cleft, and drives a large conformational change in the hexamer from open to closed states (Fig. 1B). INTRO
196 202 closed protein_state During the catalytic cycle, the NBD executes a large movement, hinged around a “pivot” helix, that closes the catalytic cleft, and drives a large conformational change in the hexamer from open to closed states (Fig. 1B). INTRO
30 37 antenna structure_element The third domain, dubbed the “antenna,” is an evolutionary acquisition in protista and animals. INTRO
74 82 protista taxonomy_domain The third domain, dubbed the “antenna,” is an evolutionary acquisition in protista and animals. INTRO
87 94 animals taxonomy_domain The third domain, dubbed the “antenna,” is an evolutionary acquisition in protista and animals. INTRO
0 8 Antennae structure_element Antennae of adjacent protomers in each trimer intercalate to form a bundle, perpendicular to the pivot helices, that protrudes along the distal extremes of the 3-fold axis. INTRO
21 30 protomers oligomeric_state Antennae of adjacent protomers in each trimer intercalate to form a bundle, perpendicular to the pivot helices, that protrudes along the distal extremes of the 3-fold axis. INTRO
39 45 trimer oligomeric_state Antennae of adjacent protomers in each trimer intercalate to form a bundle, perpendicular to the pivot helices, that protrudes along the distal extremes of the 3-fold axis. INTRO
97 110 pivot helices structure_element Antennae of adjacent protomers in each trimer intercalate to form a bundle, perpendicular to the pivot helices, that protrudes along the distal extremes of the 3-fold axis. INTRO
7 15 protomer oligomeric_state When a protomer undergoes a conformational change, the rotation of its pivot helix is transferred through the antenna to the adjacent subunit. INTRO
71 82 pivot helix structure_element When a protomer undergoes a conformational change, the rotation of its pivot helix is transferred through the antenna to the adjacent subunit. INTRO
110 117 antenna structure_element When a protomer undergoes a conformational change, the rotation of its pivot helix is transferred through the antenna to the adjacent subunit. INTRO
134 141 subunit structure_element When a protomer undergoes a conformational change, the rotation of its pivot helix is transferred through the antenna to the adjacent subunit. INTRO
21 28 antenna structure_element The influence of the antenna, present only in protozoan and metazoan enzymes, has been proposed to explain its cooperative behavior, which is absent in bacterial homologs. INTRO
46 55 protozoan taxonomy_domain The influence of the antenna, present only in protozoan and metazoan enzymes, has been proposed to explain its cooperative behavior, which is absent in bacterial homologs. INTRO
60 68 metazoan taxonomy_domain The influence of the antenna, present only in protozoan and metazoan enzymes, has been proposed to explain its cooperative behavior, which is absent in bacterial homologs. INTRO
152 161 bacterial taxonomy_domain The influence of the antenna, present only in protozoan and metazoan enzymes, has been proposed to explain its cooperative behavior, which is absent in bacterial homologs. INTRO
51 54 GDH protein_type Structure and quaternary conformational changes in GDH. (A) Views of open (PDB ID 1NR7) and closed (PDB 3MW9) states of the GDH hexamer, shown in ribbon representation perpendicular to the 2-fold symmetry axis (side view, top) and 3-fold symmetry axis (top view, bottom). FIG
69 73 open protein_state Structure and quaternary conformational changes in GDH. (A) Views of open (PDB ID 1NR7) and closed (PDB 3MW9) states of the GDH hexamer, shown in ribbon representation perpendicular to the 2-fold symmetry axis (side view, top) and 3-fold symmetry axis (top view, bottom). FIG
92 98 closed protein_state Structure and quaternary conformational changes in GDH. (A) Views of open (PDB ID 1NR7) and closed (PDB 3MW9) states of the GDH hexamer, shown in ribbon representation perpendicular to the 2-fold symmetry axis (side view, top) and 3-fold symmetry axis (top view, bottom). FIG
124 127 GDH protein_type Structure and quaternary conformational changes in GDH. (A) Views of open (PDB ID 1NR7) and closed (PDB 3MW9) states of the GDH hexamer, shown in ribbon representation perpendicular to the 2-fold symmetry axis (side view, top) and 3-fold symmetry axis (top view, bottom). FIG
128 135 hexamer oligomeric_state Structure and quaternary conformational changes in GDH. (A) Views of open (PDB ID 1NR7) and closed (PDB 3MW9) states of the GDH hexamer, shown in ribbon representation perpendicular to the 2-fold symmetry axis (side view, top) and 3-fold symmetry axis (top view, bottom). FIG
11 20 protomers oligomeric_state Only three protomers are shown in the top view for purposes of visual clarity. FIG
137 141 open protein_state The dashed lines and arrows, respectively, highlight the slight extension in length, and twist in shape that occurs with transition from open to the closed state. FIG
149 155 closed protein_state The dashed lines and arrows, respectively, highlight the slight extension in length, and twist in shape that occurs with transition from open to the closed state. FIG
4 8 open protein_state The open state shown is for unliganded GDH, whereas the closed state has NADH, GTP, and glutamate bound. (B) Superposition of structures for closed and open conformations, along with a series of possible intermediate conformations along the trajectory that serve to illustrate the extent of change in structure across different regions of the protein. FIG
28 38 unliganded protein_state The open state shown is for unliganded GDH, whereas the closed state has NADH, GTP, and glutamate bound. (B) Superposition of structures for closed and open conformations, along with a series of possible intermediate conformations along the trajectory that serve to illustrate the extent of change in structure across different regions of the protein. FIG
39 42 GDH protein_type The open state shown is for unliganded GDH, whereas the closed state has NADH, GTP, and glutamate bound. (B) Superposition of structures for closed and open conformations, along with a series of possible intermediate conformations along the trajectory that serve to illustrate the extent of change in structure across different regions of the protein. FIG
56 62 closed protein_state The open state shown is for unliganded GDH, whereas the closed state has NADH, GTP, and glutamate bound. (B) Superposition of structures for closed and open conformations, along with a series of possible intermediate conformations along the trajectory that serve to illustrate the extent of change in structure across different regions of the protein. FIG
73 77 NADH chemical The open state shown is for unliganded GDH, whereas the closed state has NADH, GTP, and glutamate bound. (B) Superposition of structures for closed and open conformations, along with a series of possible intermediate conformations along the trajectory that serve to illustrate the extent of change in structure across different regions of the protein. FIG
79 82 GTP chemical The open state shown is for unliganded GDH, whereas the closed state has NADH, GTP, and glutamate bound. (B) Superposition of structures for closed and open conformations, along with a series of possible intermediate conformations along the trajectory that serve to illustrate the extent of change in structure across different regions of the protein. FIG
88 97 glutamate chemical The open state shown is for unliganded GDH, whereas the closed state has NADH, GTP, and glutamate bound. (B) Superposition of structures for closed and open conformations, along with a series of possible intermediate conformations along the trajectory that serve to illustrate the extent of change in structure across different regions of the protein. FIG
98 103 bound protein_state The open state shown is for unliganded GDH, whereas the closed state has NADH, GTP, and glutamate bound. (B) Superposition of structures for closed and open conformations, along with a series of possible intermediate conformations along the trajectory that serve to illustrate the extent of change in structure across different regions of the protein. FIG
109 122 Superposition experimental_method The open state shown is for unliganded GDH, whereas the closed state has NADH, GTP, and glutamate bound. (B) Superposition of structures for closed and open conformations, along with a series of possible intermediate conformations along the trajectory that serve to illustrate the extent of change in structure across different regions of the protein. FIG
126 136 structures evidence The open state shown is for unliganded GDH, whereas the closed state has NADH, GTP, and glutamate bound. (B) Superposition of structures for closed and open conformations, along with a series of possible intermediate conformations along the trajectory that serve to illustrate the extent of change in structure across different regions of the protein. FIG
141 147 closed protein_state The open state shown is for unliganded GDH, whereas the closed state has NADH, GTP, and glutamate bound. (B) Superposition of structures for closed and open conformations, along with a series of possible intermediate conformations along the trajectory that serve to illustrate the extent of change in structure across different regions of the protein. FIG
152 156 open protein_state The open state shown is for unliganded GDH, whereas the closed state has NADH, GTP, and glutamate bound. (B) Superposition of structures for closed and open conformations, along with a series of possible intermediate conformations along the trajectory that serve to illustrate the extent of change in structure across different regions of the protein. FIG
24 30 closed protein_state The transition between “closed” and “open” states of GDH is modulated by two allosteric sites in each protomer (Fig. 1A), which are differentially bound by GTP (an inhibitor) and ADP (an activator). INTRO
37 41 open protein_state The transition between “closed” and “open” states of GDH is modulated by two allosteric sites in each protomer (Fig. 1A), which are differentially bound by GTP (an inhibitor) and ADP (an activator). INTRO
53 56 GDH protein_type The transition between “closed” and “open” states of GDH is modulated by two allosteric sites in each protomer (Fig. 1A), which are differentially bound by GTP (an inhibitor) and ADP (an activator). INTRO
77 93 allosteric sites site The transition between “closed” and “open” states of GDH is modulated by two allosteric sites in each protomer (Fig. 1A), which are differentially bound by GTP (an inhibitor) and ADP (an activator). INTRO
102 110 protomer oligomeric_state The transition between “closed” and “open” states of GDH is modulated by two allosteric sites in each protomer (Fig. 1A), which are differentially bound by GTP (an inhibitor) and ADP (an activator). INTRO
147 155 bound by protein_state The transition between “closed” and “open” states of GDH is modulated by two allosteric sites in each protomer (Fig. 1A), which are differentially bound by GTP (an inhibitor) and ADP (an activator). INTRO
156 159 GTP chemical The transition between “closed” and “open” states of GDH is modulated by two allosteric sites in each protomer (Fig. 1A), which are differentially bound by GTP (an inhibitor) and ADP (an activator). INTRO
179 182 ADP chemical The transition between “closed” and “open” states of GDH is modulated by two allosteric sites in each protomer (Fig. 1A), which are differentially bound by GTP (an inhibitor) and ADP (an activator). INTRO
44 47 GDH protein_type These allosteric modulators tightly control GDH function in vivo. INTRO
42 53 pivot helix structure_element In the first site, which sits next to the pivot helix at the base of the antenna (the “GTP binding site”), GTP binding is known to act as an inhibitor, preventing release of the reaction product from the catalytic site by stabilizing the closed conformation of the catalytic cleft. INTRO
73 80 antenna structure_element In the first site, which sits next to the pivot helix at the base of the antenna (the “GTP binding site”), GTP binding is known to act as an inhibitor, preventing release of the reaction product from the catalytic site by stabilizing the closed conformation of the catalytic cleft. INTRO
87 103 GTP binding site site In the first site, which sits next to the pivot helix at the base of the antenna (the “GTP binding site”), GTP binding is known to act as an inhibitor, preventing release of the reaction product from the catalytic site by stabilizing the closed conformation of the catalytic cleft. INTRO
107 110 GTP chemical In the first site, which sits next to the pivot helix at the base of the antenna (the “GTP binding site”), GTP binding is known to act as an inhibitor, preventing release of the reaction product from the catalytic site by stabilizing the closed conformation of the catalytic cleft. INTRO
204 218 catalytic site site In the first site, which sits next to the pivot helix at the base of the antenna (the “GTP binding site”), GTP binding is known to act as an inhibitor, preventing release of the reaction product from the catalytic site by stabilizing the closed conformation of the catalytic cleft. INTRO
238 244 closed protein_state In the first site, which sits next to the pivot helix at the base of the antenna (the “GTP binding site”), GTP binding is known to act as an inhibitor, preventing release of the reaction product from the catalytic site by stabilizing the closed conformation of the catalytic cleft. INTRO
265 280 catalytic cleft site In the first site, which sits next to the pivot helix at the base of the antenna (the “GTP binding site”), GTP binding is known to act as an inhibitor, preventing release of the reaction product from the catalytic site by stabilizing the closed conformation of the catalytic cleft. INTRO
15 30 regulatory site site In the second “regulatory site”, which is situated near the pivot helix between adjacent protomers, ADP acts as an activator of enzymatic activity, presumably by hastening the opening of the catalytic cleft that leads to the release of the reaction product. INTRO
60 71 pivot helix structure_element In the second “regulatory site”, which is situated near the pivot helix between adjacent protomers, ADP acts as an activator of enzymatic activity, presumably by hastening the opening of the catalytic cleft that leads to the release of the reaction product. INTRO
89 98 protomers oligomeric_state In the second “regulatory site”, which is situated near the pivot helix between adjacent protomers, ADP acts as an activator of enzymatic activity, presumably by hastening the opening of the catalytic cleft that leads to the release of the reaction product. INTRO
100 103 ADP chemical In the second “regulatory site”, which is situated near the pivot helix between adjacent protomers, ADP acts as an activator of enzymatic activity, presumably by hastening the opening of the catalytic cleft that leads to the release of the reaction product. INTRO
191 206 catalytic cleft site In the second “regulatory site”, which is situated near the pivot helix between adjacent protomers, ADP acts as an activator of enzymatic activity, presumably by hastening the opening of the catalytic cleft that leads to the release of the reaction product. INTRO
56 60 NADH chemical Interestingly, it has also been shown that the coenzyme NADH can bind to the regulatory site (also bound by the activator ADP), exerting a converse, inhibitory effect on GDH product release, although the role this may play in vivo is not entirely clear. INTRO
77 92 regulatory site site Interestingly, it has also been shown that the coenzyme NADH can bind to the regulatory site (also bound by the activator ADP), exerting a converse, inhibitory effect on GDH product release, although the role this may play in vivo is not entirely clear. INTRO
99 107 bound by protein_state Interestingly, it has also been shown that the coenzyme NADH can bind to the regulatory site (also bound by the activator ADP), exerting a converse, inhibitory effect on GDH product release, although the role this may play in vivo is not entirely clear. INTRO
122 125 ADP chemical Interestingly, it has also been shown that the coenzyme NADH can bind to the regulatory site (also bound by the activator ADP), exerting a converse, inhibitory effect on GDH product release, although the role this may play in vivo is not entirely clear. INTRO
170 173 GDH protein_type Interestingly, it has also been shown that the coenzyme NADH can bind to the regulatory site (also bound by the activator ADP), exerting a converse, inhibitory effect on GDH product release, although the role this may play in vivo is not entirely clear. INTRO
28 46 crystal structures evidence Although there are numerous crystal structures available for GDH in complex with cofactors and nucleotides, they are limited to the combinations that have been amenable to crystallization. INTRO
61 64 GDH protein_type Although there are numerous crystal structures available for GDH in complex with cofactors and nucleotides, they are limited to the combinations that have been amenable to crystallization. INTRO
65 80 in complex with protein_state Although there are numerous crystal structures available for GDH in complex with cofactors and nucleotides, they are limited to the combinations that have been amenable to crystallization. INTRO
172 187 crystallization experimental_method Although there are numerous crystal structures available for GDH in complex with cofactors and nucleotides, they are limited to the combinations that have been amenable to crystallization. INTRO
11 16 X-ray experimental_method Nearly all X-ray structures of mammalian GDH are in the closed conformation, and the few structures that are in the open conformation are at lower resolution (Table 1). INTRO
17 27 structures evidence Nearly all X-ray structures of mammalian GDH are in the closed conformation, and the few structures that are in the open conformation are at lower resolution (Table 1). INTRO
31 40 mammalian taxonomy_domain Nearly all X-ray structures of mammalian GDH are in the closed conformation, and the few structures that are in the open conformation are at lower resolution (Table 1). INTRO
41 44 GDH protein_type Nearly all X-ray structures of mammalian GDH are in the closed conformation, and the few structures that are in the open conformation are at lower resolution (Table 1). INTRO
56 62 closed protein_state Nearly all X-ray structures of mammalian GDH are in the closed conformation, and the few structures that are in the open conformation are at lower resolution (Table 1). INTRO
89 99 structures evidence Nearly all X-ray structures of mammalian GDH are in the closed conformation, and the few structures that are in the open conformation are at lower resolution (Table 1). INTRO
116 120 open protein_state Nearly all X-ray structures of mammalian GDH are in the closed conformation, and the few structures that are in the open conformation are at lower resolution (Table 1). INTRO
9 19 structures evidence Of those structures in the closed conformation, most include NAD[P]H, GTP, and glutamate (or, alternately, NAD+, GTP, and α-ketoglutarate). INTRO
27 33 closed protein_state Of those structures in the closed conformation, most include NAD[P]H, GTP, and glutamate (or, alternately, NAD+, GTP, and α-ketoglutarate). INTRO
61 68 NAD[P]H chemical Of those structures in the closed conformation, most include NAD[P]H, GTP, and glutamate (or, alternately, NAD+, GTP, and α-ketoglutarate). INTRO
70 73 GTP chemical Of those structures in the closed conformation, most include NAD[P]H, GTP, and glutamate (or, alternately, NAD+, GTP, and α-ketoglutarate). INTRO
79 88 glutamate chemical Of those structures in the closed conformation, most include NAD[P]H, GTP, and glutamate (or, alternately, NAD+, GTP, and α-ketoglutarate). INTRO
107 111 NAD+ chemical Of those structures in the closed conformation, most include NAD[P]H, GTP, and glutamate (or, alternately, NAD+, GTP, and α-ketoglutarate). INTRO
113 116 GTP chemical Of those structures in the closed conformation, most include NAD[P]H, GTP, and glutamate (or, alternately, NAD+, GTP, and α-ketoglutarate). INTRO
122 137 α-ketoglutarate chemical Of those structures in the closed conformation, most include NAD[P]H, GTP, and glutamate (or, alternately, NAD+, GTP, and α-ketoglutarate). INTRO
37 40 GTP chemical However, the effects of coenzyme and GTP, bound alone or in concert in the absence of glutamate, have not been analyzed by crystallographic methods. INTRO
42 53 bound alone protein_state However, the effects of coenzyme and GTP, bound alone or in concert in the absence of glutamate, have not been analyzed by crystallographic methods. INTRO
75 85 absence of protein_state However, the effects of coenzyme and GTP, bound alone or in concert in the absence of glutamate, have not been analyzed by crystallographic methods. INTRO
86 95 glutamate chemical However, the effects of coenzyme and GTP, bound alone or in concert in the absence of glutamate, have not been analyzed by crystallographic methods. INTRO
16 56 single-particle cryo-electron microscopy experimental_method Here, we report single-particle cryo-electron microscopy (cryo-EM) studies that show that under these conditions enzyme complexes coexist in both closed and open conformations. INTRO
58 65 cryo-EM experimental_method Here, we report single-particle cryo-electron microscopy (cryo-EM) studies that show that under these conditions enzyme complexes coexist in both closed and open conformations. INTRO
146 152 closed protein_state Here, we report single-particle cryo-electron microscopy (cryo-EM) studies that show that under these conditions enzyme complexes coexist in both closed and open conformations. INTRO
157 161 open protein_state Here, we report single-particle cryo-electron microscopy (cryo-EM) studies that show that under these conditions enzyme complexes coexist in both closed and open conformations. INTRO
17 27 structures evidence We show that the structures in both states can be resolved at near-atomic resolution, suggesting a molecular mechanism for synergistic inhibition of GDH by NADH and GTP (see Table 2 for detailed information on all cryo-EM-derived structures that we report in this work). INTRO
149 152 GDH protein_type We show that the structures in both states can be resolved at near-atomic resolution, suggesting a molecular mechanism for synergistic inhibition of GDH by NADH and GTP (see Table 2 for detailed information on all cryo-EM-derived structures that we report in this work). INTRO
156 160 NADH chemical We show that the structures in both states can be resolved at near-atomic resolution, suggesting a molecular mechanism for synergistic inhibition of GDH by NADH and GTP (see Table 2 for detailed information on all cryo-EM-derived structures that we report in this work). INTRO
165 168 GTP chemical We show that the structures in both states can be resolved at near-atomic resolution, suggesting a molecular mechanism for synergistic inhibition of GDH by NADH and GTP (see Table 2 for detailed information on all cryo-EM-derived structures that we report in this work). INTRO
214 221 cryo-EM experimental_method We show that the structures in both states can be resolved at near-atomic resolution, suggesting a molecular mechanism for synergistic inhibition of GDH by NADH and GTP (see Table 2 for detailed information on all cryo-EM-derived structures that we report in this work). INTRO
230 240 structures evidence We show that the structures in both states can be resolved at near-atomic resolution, suggesting a molecular mechanism for synergistic inhibition of GDH by NADH and GTP (see Table 2 for detailed information on all cryo-EM-derived structures that we report in this work). INTRO
0 5 X-ray experimental_method X-ray structures of mammalian GDH reported in both the open and closed conformations TABLE
6 16 structures evidence X-ray structures of mammalian GDH reported in both the open and closed conformations TABLE
20 29 mammalian taxonomy_domain X-ray structures of mammalian GDH reported in both the open and closed conformations TABLE
30 33 GDH protein_type X-ray structures of mammalian GDH reported in both the open and closed conformations TABLE
55 59 open protein_state X-ray structures of mammalian GDH reported in both the open and closed conformations TABLE
64 70 closed protein_state X-ray structures of mammalian GDH reported in both the open and closed conformations TABLE
0 3 GDH protein "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
45 47 WT protein_state "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
48 52 NADH chemical "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
55 58 GLU chemical "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
61 64 GTP chemical "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
70 76 Closed protein_state "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
83 85 WT protein_state "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
86 89 Glu chemical "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
91 94 GTP chemical "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
96 101 NADPH chemical "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
122 128 Closed protein_state "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
135 137 WT protein_state "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
138 141 Glu chemical "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
143 148 NADPH chemical "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
150 153 GTP chemical "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
168 174 Closed protein_state "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
181 183 WT protein_state "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
184 187 apo protein_state "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
193 197 Open protein_state "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
204 206 WT protein_state "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
207 212 NADPH chemical "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
214 223 glutamate chemical "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
229 232 GTP chemical "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
238 244 Closed protein_state "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
251 253 WT protein_state "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
254 259 NADPH chemical "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
262 265 GLU chemical "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
268 271 GTP chemical "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
274 278 Zinc chemical "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
284 290 Closed protein_state "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
298 300 WT protein_state "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
301 306 NADPH chemical "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
308 311 Glu chemical "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
313 316 GTP chemical "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
339 345 Closed protein_state "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
350 352 WT protein_state "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
353 356 NAD chemical "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
358 361 PO4 chemical "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
367 381 2-oxoglutarate chemical "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
387 393 Closed protein_state "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
400 402 WT protein_state "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
403 408 NADPH chemical "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
411 414 GLU chemical "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
425 431 Closed protein_state "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
445 451 mutant protein_state "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
452 455 apo protein_state "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
461 465 Open protein_state "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
472 474 WT protein_state "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
475 478 apo protein_state "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
484 488 Open protein_state "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
495 497 WT protein_state "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
498 501 ADP chemical "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
507 511 Open protein_state "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
518 520 WT protein_state "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
521 526 NADPH chemical "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
564 568 Open protein_state "GDH Ligands PDB ID Conformation Resolution WT NADH + GLU + GTP 3MW9 Closed 2.4 WT Glu, GTP, NADPH, and Bithionol 3ETD Closed 2.5 WT Glu, NADPH, GTP + GW5074 3ETG Closed 2.5 WT apo 1L1F Open 2.7 WT NADPH, glutamate, and GTP 1HWZ Closed 2.8 WT NADPH + GLU + GTP + Zinc 3MVQ Closed 2.94 WT NADPH, Glu, GTP, Hexachlorophene 3ETE Closed 3 WT NAD, PO4, and 2-oxoglutarate 1HWY Closed 3.2 WT NADPH + GLU + Eu 3MVO Closed 3.23 R463A mutant apo 1NR1 Open 3.3 WT apo 1NR7 Open 3.3 WT ADP 1NQT Open 3.5 WT NADPH and Epicatechin-3-gallate (Ecg) 3QMU Open 3.62 " TABLE
0 7 Cryo-EM experimental_method Cryo-EM structures of mammalian GDH determined for this study TABLE
8 18 structures evidence Cryo-EM structures of mammalian GDH determined for this study TABLE
22 31 mammalian taxonomy_domain Cryo-EM structures of mammalian GDH determined for this study TABLE
32 35 GDH protein_type Cryo-EM structures of mammalian GDH determined for this study TABLE
0 3 GDH protein_type "GDH Ligands EMDB ID PDB ID Conformation Resolution Particles WT apo EMD-6630 3JCZ Open 3.26 22462 WT GTP EMD-6631 3JD0 Open 3.47 39439 WT NADH EMD-6635 3JD2 Open 3.27 34716 WT NADH EMD-6634 3JD1 Closed 3.27 34926 WT NADH + GTP EMD-6632 3JD3 Open 3.55 14793 WT NADH + GTP EMD-6633 3JD4 Closed 3.40 20429 " TABLE
63 65 WT protein_state "GDH Ligands EMDB ID PDB ID Conformation Resolution Particles WT apo EMD-6630 3JCZ Open 3.26 22462 WT GTP EMD-6631 3JD0 Open 3.47 39439 WT NADH EMD-6635 3JD2 Open 3.27 34716 WT NADH EMD-6634 3JD1 Closed 3.27 34926 WT NADH + GTP EMD-6632 3JD3 Open 3.55 14793 WT NADH + GTP EMD-6633 3JD4 Closed 3.40 20429 " TABLE
66 69 apo protein_state "GDH Ligands EMDB ID PDB ID Conformation Resolution Particles WT apo EMD-6630 3JCZ Open 3.26 22462 WT GTP EMD-6631 3JD0 Open 3.47 39439 WT NADH EMD-6635 3JD2 Open 3.27 34716 WT NADH EMD-6634 3JD1 Closed 3.27 34926 WT NADH + GTP EMD-6632 3JD3 Open 3.55 14793 WT NADH + GTP EMD-6633 3JD4 Closed 3.40 20429 " TABLE
84 88 Open protein_state "GDH Ligands EMDB ID PDB ID Conformation Resolution Particles WT apo EMD-6630 3JCZ Open 3.26 22462 WT GTP EMD-6631 3JD0 Open 3.47 39439 WT NADH EMD-6635 3JD2 Open 3.27 34716 WT NADH EMD-6634 3JD1 Closed 3.27 34926 WT NADH + GTP EMD-6632 3JD3 Open 3.55 14793 WT NADH + GTP EMD-6633 3JD4 Closed 3.40 20429 " TABLE
102 104 WT protein_state "GDH Ligands EMDB ID PDB ID Conformation Resolution Particles WT apo EMD-6630 3JCZ Open 3.26 22462 WT GTP EMD-6631 3JD0 Open 3.47 39439 WT NADH EMD-6635 3JD2 Open 3.27 34716 WT NADH EMD-6634 3JD1 Closed 3.27 34926 WT NADH + GTP EMD-6632 3JD3 Open 3.55 14793 WT NADH + GTP EMD-6633 3JD4 Closed 3.40 20429 " TABLE
105 108 GTP chemical "GDH Ligands EMDB ID PDB ID Conformation Resolution Particles WT apo EMD-6630 3JCZ Open 3.26 22462 WT GTP EMD-6631 3JD0 Open 3.47 39439 WT NADH EMD-6635 3JD2 Open 3.27 34716 WT NADH EMD-6634 3JD1 Closed 3.27 34926 WT NADH + GTP EMD-6632 3JD3 Open 3.55 14793 WT NADH + GTP EMD-6633 3JD4 Closed 3.40 20429 " TABLE
123 127 Open protein_state "GDH Ligands EMDB ID PDB ID Conformation Resolution Particles WT apo EMD-6630 3JCZ Open 3.26 22462 WT GTP EMD-6631 3JD0 Open 3.47 39439 WT NADH EMD-6635 3JD2 Open 3.27 34716 WT NADH EMD-6634 3JD1 Closed 3.27 34926 WT NADH + GTP EMD-6632 3JD3 Open 3.55 14793 WT NADH + GTP EMD-6633 3JD4 Closed 3.40 20429 " TABLE
141 143 WT protein_state "GDH Ligands EMDB ID PDB ID Conformation Resolution Particles WT apo EMD-6630 3JCZ Open 3.26 22462 WT GTP EMD-6631 3JD0 Open 3.47 39439 WT NADH EMD-6635 3JD2 Open 3.27 34716 WT NADH EMD-6634 3JD1 Closed 3.27 34926 WT NADH + GTP EMD-6632 3JD3 Open 3.55 14793 WT NADH + GTP EMD-6633 3JD4 Closed 3.40 20429 " TABLE
144 148 NADH chemical "GDH Ligands EMDB ID PDB ID Conformation Resolution Particles WT apo EMD-6630 3JCZ Open 3.26 22462 WT GTP EMD-6631 3JD0 Open 3.47 39439 WT NADH EMD-6635 3JD2 Open 3.27 34716 WT NADH EMD-6634 3JD1 Closed 3.27 34926 WT NADH + GTP EMD-6632 3JD3 Open 3.55 14793 WT NADH + GTP EMD-6633 3JD4 Closed 3.40 20429 " TABLE
163 167 Open protein_state "GDH Ligands EMDB ID PDB ID Conformation Resolution Particles WT apo EMD-6630 3JCZ Open 3.26 22462 WT GTP EMD-6631 3JD0 Open 3.47 39439 WT NADH EMD-6635 3JD2 Open 3.27 34716 WT NADH EMD-6634 3JD1 Closed 3.27 34926 WT NADH + GTP EMD-6632 3JD3 Open 3.55 14793 WT NADH + GTP EMD-6633 3JD4 Closed 3.40 20429 " TABLE
181 183 WT protein_state "GDH Ligands EMDB ID PDB ID Conformation Resolution Particles WT apo EMD-6630 3JCZ Open 3.26 22462 WT GTP EMD-6631 3JD0 Open 3.47 39439 WT NADH EMD-6635 3JD2 Open 3.27 34716 WT NADH EMD-6634 3JD1 Closed 3.27 34926 WT NADH + GTP EMD-6632 3JD3 Open 3.55 14793 WT NADH + GTP EMD-6633 3JD4 Closed 3.40 20429 " TABLE
184 188 NADH chemical "GDH Ligands EMDB ID PDB ID Conformation Resolution Particles WT apo EMD-6630 3JCZ Open 3.26 22462 WT GTP EMD-6631 3JD0 Open 3.47 39439 WT NADH EMD-6635 3JD2 Open 3.27 34716 WT NADH EMD-6634 3JD1 Closed 3.27 34926 WT NADH + GTP EMD-6632 3JD3 Open 3.55 14793 WT NADH + GTP EMD-6633 3JD4 Closed 3.40 20429 " TABLE
203 209 Closed protein_state "GDH Ligands EMDB ID PDB ID Conformation Resolution Particles WT apo EMD-6630 3JCZ Open 3.26 22462 WT GTP EMD-6631 3JD0 Open 3.47 39439 WT NADH EMD-6635 3JD2 Open 3.27 34716 WT NADH EMD-6634 3JD1 Closed 3.27 34926 WT NADH + GTP EMD-6632 3JD3 Open 3.55 14793 WT NADH + GTP EMD-6633 3JD4 Closed 3.40 20429 " TABLE
223 225 WT protein_state "GDH Ligands EMDB ID PDB ID Conformation Resolution Particles WT apo EMD-6630 3JCZ Open 3.26 22462 WT GTP EMD-6631 3JD0 Open 3.47 39439 WT NADH EMD-6635 3JD2 Open 3.27 34716 WT NADH EMD-6634 3JD1 Closed 3.27 34926 WT NADH + GTP EMD-6632 3JD3 Open 3.55 14793 WT NADH + GTP EMD-6633 3JD4 Closed 3.40 20429 " TABLE
226 230 NADH chemical "GDH Ligands EMDB ID PDB ID Conformation Resolution Particles WT apo EMD-6630 3JCZ Open 3.26 22462 WT GTP EMD-6631 3JD0 Open 3.47 39439 WT NADH EMD-6635 3JD2 Open 3.27 34716 WT NADH EMD-6634 3JD1 Closed 3.27 34926 WT NADH + GTP EMD-6632 3JD3 Open 3.55 14793 WT NADH + GTP EMD-6633 3JD4 Closed 3.40 20429 " TABLE
233 236 GTP chemical "GDH Ligands EMDB ID PDB ID Conformation Resolution Particles WT apo EMD-6630 3JCZ Open 3.26 22462 WT GTP EMD-6631 3JD0 Open 3.47 39439 WT NADH EMD-6635 3JD2 Open 3.27 34716 WT NADH EMD-6634 3JD1 Closed 3.27 34926 WT NADH + GTP EMD-6632 3JD3 Open 3.55 14793 WT NADH + GTP EMD-6633 3JD4 Closed 3.40 20429 " TABLE
251 255 Open protein_state "GDH Ligands EMDB ID PDB ID Conformation Resolution Particles WT apo EMD-6630 3JCZ Open 3.26 22462 WT GTP EMD-6631 3JD0 Open 3.47 39439 WT NADH EMD-6635 3JD2 Open 3.27 34716 WT NADH EMD-6634 3JD1 Closed 3.27 34926 WT NADH + GTP EMD-6632 3JD3 Open 3.55 14793 WT NADH + GTP EMD-6633 3JD4 Closed 3.40 20429 " TABLE
269 271 WT protein_state "GDH Ligands EMDB ID PDB ID Conformation Resolution Particles WT apo EMD-6630 3JCZ Open 3.26 22462 WT GTP EMD-6631 3JD0 Open 3.47 39439 WT NADH EMD-6635 3JD2 Open 3.27 34716 WT NADH EMD-6634 3JD1 Closed 3.27 34926 WT NADH + GTP EMD-6632 3JD3 Open 3.55 14793 WT NADH + GTP EMD-6633 3JD4 Closed 3.40 20429 " TABLE
272 276 NADH chemical "GDH Ligands EMDB ID PDB ID Conformation Resolution Particles WT apo EMD-6630 3JCZ Open 3.26 22462 WT GTP EMD-6631 3JD0 Open 3.47 39439 WT NADH EMD-6635 3JD2 Open 3.27 34716 WT NADH EMD-6634 3JD1 Closed 3.27 34926 WT NADH + GTP EMD-6632 3JD3 Open 3.55 14793 WT NADH + GTP EMD-6633 3JD4 Closed 3.40 20429 " TABLE
279 282 GTP chemical "GDH Ligands EMDB ID PDB ID Conformation Resolution Particles WT apo EMD-6630 3JCZ Open 3.26 22462 WT GTP EMD-6631 3JD0 Open 3.47 39439 WT NADH EMD-6635 3JD2 Open 3.27 34716 WT NADH EMD-6634 3JD1 Closed 3.27 34926 WT NADH + GTP EMD-6632 3JD3 Open 3.55 14793 WT NADH + GTP EMD-6633 3JD4 Closed 3.40 20429 " TABLE
297 303 Closed protein_state "GDH Ligands EMDB ID PDB ID Conformation Resolution Particles WT apo EMD-6630 3JCZ Open 3.26 22462 WT GTP EMD-6631 3JD0 Open 3.47 39439 WT NADH EMD-6635 3JD2 Open 3.27 34716 WT NADH EMD-6634 3JD1 Closed 3.27 34926 WT NADH + GTP EMD-6632 3JD3 Open 3.55 14793 WT NADH + GTP EMD-6633 3JD4 Closed 3.40 20429 " TABLE
43 46 apo protein_state To explore the conformational landscape of apo-GDH, we first determined its structure in the absence of any added ligands (Supplemental Fig. 1, Fig. 2, A–C). RESULTS
47 50 GDH protein To explore the conformational landscape of apo-GDH, we first determined its structure in the absence of any added ligands (Supplemental Fig. 1, Fig. 2, A–C). RESULTS
76 85 structure evidence To explore the conformational landscape of apo-GDH, we first determined its structure in the absence of any added ligands (Supplemental Fig. 1, Fig. 2, A–C). RESULTS
93 103 absence of protein_state To explore the conformational landscape of apo-GDH, we first determined its structure in the absence of any added ligands (Supplemental Fig. 1, Fig. 2, A–C). RESULTS
4 15 density map evidence The density map, refined to an average resolution of ∼3.0 Å (Supplemental Fig. 2), is in the open conformation and closely matches the model of unliganded GDH derived by X-ray crystallography at 3.3 Å resolution (PDB ID 1NR7). RESULTS
93 97 open protein_state The density map, refined to an average resolution of ∼3.0 Å (Supplemental Fig. 2), is in the open conformation and closely matches the model of unliganded GDH derived by X-ray crystallography at 3.3 Å resolution (PDB ID 1NR7). RESULTS
144 154 unliganded protein_state The density map, refined to an average resolution of ∼3.0 Å (Supplemental Fig. 2), is in the open conformation and closely matches the model of unliganded GDH derived by X-ray crystallography at 3.3 Å resolution (PDB ID 1NR7). RESULTS
155 158 GDH protein The density map, refined to an average resolution of ∼3.0 Å (Supplemental Fig. 2), is in the open conformation and closely matches the model of unliganded GDH derived by X-ray crystallography at 3.3 Å resolution (PDB ID 1NR7). RESULTS
170 191 X-ray crystallography experimental_method The density map, refined to an average resolution of ∼3.0 Å (Supplemental Fig. 2), is in the open conformation and closely matches the model of unliganded GDH derived by X-ray crystallography at 3.3 Å resolution (PDB ID 1NR7). RESULTS
81 87 ResMap experimental_method The variation in local resolution from the core to the periphery, as reported by ResMap (Supplemental Fig. 3D), is consistent with the B-factor gradient observed in the crystal structure (Supplemental Fig. 3A). RESULTS
135 152 B-factor gradient evidence The variation in local resolution from the core to the periphery, as reported by ResMap (Supplemental Fig. 3D), is consistent with the B-factor gradient observed in the crystal structure (Supplemental Fig. 3A). RESULTS
169 186 crystal structure evidence The variation in local resolution from the core to the periphery, as reported by ResMap (Supplemental Fig. 3D), is consistent with the B-factor gradient observed in the crystal structure (Supplemental Fig. 3A). RESULTS
64 68 open protein_state Extensive classification without imposing symmetry yielded only open structures and failed to detect any closed catalytic cleft in the unliganded enzyme, suggesting that all six protomers are in the open conformation. RESULTS
69 79 structures evidence Extensive classification without imposing symmetry yielded only open structures and failed to detect any closed catalytic cleft in the unliganded enzyme, suggesting that all six protomers are in the open conformation. RESULTS
105 111 closed protein_state Extensive classification without imposing symmetry yielded only open structures and failed to detect any closed catalytic cleft in the unliganded enzyme, suggesting that all six protomers are in the open conformation. RESULTS
112 127 catalytic cleft site Extensive classification without imposing symmetry yielded only open structures and failed to detect any closed catalytic cleft in the unliganded enzyme, suggesting that all six protomers are in the open conformation. RESULTS
135 145 unliganded protein_state Extensive classification without imposing symmetry yielded only open structures and failed to detect any closed catalytic cleft in the unliganded enzyme, suggesting that all six protomers are in the open conformation. RESULTS
178 187 protomers oligomeric_state Extensive classification without imposing symmetry yielded only open structures and failed to detect any closed catalytic cleft in the unliganded enzyme, suggesting that all six protomers are in the open conformation. RESULTS
199 203 open protein_state Extensive classification without imposing symmetry yielded only open structures and failed to detect any closed catalytic cleft in the unliganded enzyme, suggesting that all six protomers are in the open conformation. RESULTS
37 42 loops structure_element Consistent with this conclusion, the loops connecting the β-strands of the Rossmann fold are well-defined (Fig. 2B), implying that there is little movement at the NBD, as the transition between closed and open states is associated with NBD movement (Fig. 1B). RESULTS
58 67 β-strands structure_element Consistent with this conclusion, the loops connecting the β-strands of the Rossmann fold are well-defined (Fig. 2B), implying that there is little movement at the NBD, as the transition between closed and open states is associated with NBD movement (Fig. 1B). RESULTS
75 88 Rossmann fold structure_element Consistent with this conclusion, the loops connecting the β-strands of the Rossmann fold are well-defined (Fig. 2B), implying that there is little movement at the NBD, as the transition between closed and open states is associated with NBD movement (Fig. 1B). RESULTS
163 166 NBD structure_element Consistent with this conclusion, the loops connecting the β-strands of the Rossmann fold are well-defined (Fig. 2B), implying that there is little movement at the NBD, as the transition between closed and open states is associated with NBD movement (Fig. 1B). RESULTS
194 200 closed protein_state Consistent with this conclusion, the loops connecting the β-strands of the Rossmann fold are well-defined (Fig. 2B), implying that there is little movement at the NBD, as the transition between closed and open states is associated with NBD movement (Fig. 1B). RESULTS
205 209 open protein_state Consistent with this conclusion, the loops connecting the β-strands of the Rossmann fold are well-defined (Fig. 2B), implying that there is little movement at the NBD, as the transition between closed and open states is associated with NBD movement (Fig. 1B). RESULTS
236 239 NBD structure_element Consistent with this conclusion, the loops connecting the β-strands of the Rossmann fold are well-defined (Fig. 2B), implying that there is little movement at the NBD, as the transition between closed and open states is associated with NBD movement (Fig. 1B). RESULTS
0 7 Cryo-EM experimental_method Cryo-EM structures of GDH in unliganded and NADH-bound states. (A) Refined cryo-EM map of unliganded GDH at ∼3 Å resolution. FIG
8 18 structures evidence Cryo-EM structures of GDH in unliganded and NADH-bound states. (A) Refined cryo-EM map of unliganded GDH at ∼3 Å resolution. FIG
22 25 GDH protein Cryo-EM structures of GDH in unliganded and NADH-bound states. (A) Refined cryo-EM map of unliganded GDH at ∼3 Å resolution. FIG
29 39 unliganded protein_state Cryo-EM structures of GDH in unliganded and NADH-bound states. (A) Refined cryo-EM map of unliganded GDH at ∼3 Å resolution. FIG
44 54 NADH-bound protein_state Cryo-EM structures of GDH in unliganded and NADH-bound states. (A) Refined cryo-EM map of unliganded GDH at ∼3 Å resolution. FIG
75 82 cryo-EM experimental_method Cryo-EM structures of GDH in unliganded and NADH-bound states. (A) Refined cryo-EM map of unliganded GDH at ∼3 Å resolution. FIG
83 86 map evidence Cryo-EM structures of GDH in unliganded and NADH-bound states. (A) Refined cryo-EM map of unliganded GDH at ∼3 Å resolution. FIG
90 100 unliganded protein_state Cryo-EM structures of GDH in unliganded and NADH-bound states. (A) Refined cryo-EM map of unliganded GDH at ∼3 Å resolution. FIG
101 104 GDH protein Cryo-EM structures of GDH in unliganded and NADH-bound states. (A) Refined cryo-EM map of unliganded GDH at ∼3 Å resolution. FIG
23 34 density map evidence (B, C) Illustration of density map in the regions that contain the Rossmann nucleotide binding fold (B), pivot and antenna helices (C) in the unliganded GDH map. (D) Cryo-EM-derived density maps for two coexisting conformations that are present when GDH is bound to the cofactor NADH. FIG
67 99 Rossmann nucleotide binding fold structure_element (B, C) Illustration of density map in the regions that contain the Rossmann nucleotide binding fold (B), pivot and antenna helices (C) in the unliganded GDH map. (D) Cryo-EM-derived density maps for two coexisting conformations that are present when GDH is bound to the cofactor NADH. FIG
105 130 pivot and antenna helices structure_element (B, C) Illustration of density map in the regions that contain the Rossmann nucleotide binding fold (B), pivot and antenna helices (C) in the unliganded GDH map. (D) Cryo-EM-derived density maps for two coexisting conformations that are present when GDH is bound to the cofactor NADH. FIG
142 152 unliganded protein_state (B, C) Illustration of density map in the regions that contain the Rossmann nucleotide binding fold (B), pivot and antenna helices (C) in the unliganded GDH map. (D) Cryo-EM-derived density maps for two coexisting conformations that are present when GDH is bound to the cofactor NADH. FIG
153 156 GDH protein (B, C) Illustration of density map in the regions that contain the Rossmann nucleotide binding fold (B), pivot and antenna helices (C) in the unliganded GDH map. (D) Cryo-EM-derived density maps for two coexisting conformations that are present when GDH is bound to the cofactor NADH. FIG
157 160 map evidence (B, C) Illustration of density map in the regions that contain the Rossmann nucleotide binding fold (B), pivot and antenna helices (C) in the unliganded GDH map. (D) Cryo-EM-derived density maps for two coexisting conformations that are present when GDH is bound to the cofactor NADH. FIG
166 173 Cryo-EM experimental_method (B, C) Illustration of density map in the regions that contain the Rossmann nucleotide binding fold (B), pivot and antenna helices (C) in the unliganded GDH map. (D) Cryo-EM-derived density maps for two coexisting conformations that are present when GDH is bound to the cofactor NADH. FIG
182 194 density maps evidence (B, C) Illustration of density map in the regions that contain the Rossmann nucleotide binding fold (B), pivot and antenna helices (C) in the unliganded GDH map. (D) Cryo-EM-derived density maps for two coexisting conformations that are present when GDH is bound to the cofactor NADH. FIG
250 253 GDH protein (B, C) Illustration of density map in the regions that contain the Rossmann nucleotide binding fold (B), pivot and antenna helices (C) in the unliganded GDH map. (D) Cryo-EM-derived density maps for two coexisting conformations that are present when GDH is bound to the cofactor NADH. FIG
257 265 bound to protein_state (B, C) Illustration of density map in the regions that contain the Rossmann nucleotide binding fold (B), pivot and antenna helices (C) in the unliganded GDH map. (D) Cryo-EM-derived density maps for two coexisting conformations that are present when GDH is bound to the cofactor NADH. FIG
279 283 NADH chemical (B, C) Illustration of density map in the regions that contain the Rossmann nucleotide binding fold (B), pivot and antenna helices (C) in the unliganded GDH map. (D) Cryo-EM-derived density maps for two coexisting conformations that are present when GDH is bound to the cofactor NADH. FIG
5 13 protomer oligomeric_state Each protomer is shown in a different color and densities for NADH bound in both regulatory (red) and catalytic (purple) sites on one protomer are indicated. FIG
48 57 densities evidence Each protomer is shown in a different color and densities for NADH bound in both regulatory (red) and catalytic (purple) sites on one protomer are indicated. FIG
62 66 NADH chemical Each protomer is shown in a different color and densities for NADH bound in both regulatory (red) and catalytic (purple) sites on one protomer are indicated. FIG
67 75 bound in protein_state Each protomer is shown in a different color and densities for NADH bound in both regulatory (red) and catalytic (purple) sites on one protomer are indicated. FIG
81 91 regulatory site Each protomer is shown in a different color and densities for NADH bound in both regulatory (red) and catalytic (purple) sites on one protomer are indicated. FIG
102 111 catalytic site Each protomer is shown in a different color and densities for NADH bound in both regulatory (red) and catalytic (purple) sites on one protomer are indicated. FIG
121 126 sites site Each protomer is shown in a different color and densities for NADH bound in both regulatory (red) and catalytic (purple) sites on one protomer are indicated. FIG
134 142 protomer oligomeric_state Each protomer is shown in a different color and densities for NADH bound in both regulatory (red) and catalytic (purple) sites on one protomer are indicated. FIG
99 103 open protein_state The overall quaternary structures of the two conformations are essentially the same as that of the open and closed states observed by X-ray crystallography. FIG
108 114 closed protein_state The overall quaternary structures of the two conformations are essentially the same as that of the open and closed states observed by X-ray crystallography. FIG
134 155 X-ray crystallography experimental_method The overall quaternary structures of the two conformations are essentially the same as that of the open and closed states observed by X-ray crystallography. FIG
5 8 GDH protein When GDH is bound to NADH, GTP, and glutamate, the enzyme adopts a closed conformation; this “abortive complex” has been determined to 2.4-Å resolution by X-ray crystallography (PDB 3MW9). RESULTS
12 20 bound to protein_state When GDH is bound to NADH, GTP, and glutamate, the enzyme adopts a closed conformation; this “abortive complex” has been determined to 2.4-Å resolution by X-ray crystallography (PDB 3MW9). RESULTS
21 25 NADH chemical When GDH is bound to NADH, GTP, and glutamate, the enzyme adopts a closed conformation; this “abortive complex” has been determined to 2.4-Å resolution by X-ray crystallography (PDB 3MW9). RESULTS
27 30 GTP chemical When GDH is bound to NADH, GTP, and glutamate, the enzyme adopts a closed conformation; this “abortive complex” has been determined to 2.4-Å resolution by X-ray crystallography (PDB 3MW9). RESULTS
36 45 glutamate chemical When GDH is bound to NADH, GTP, and glutamate, the enzyme adopts a closed conformation; this “abortive complex” has been determined to 2.4-Å resolution by X-ray crystallography (PDB 3MW9). RESULTS
67 73 closed protein_state When GDH is bound to NADH, GTP, and glutamate, the enzyme adopts a closed conformation; this “abortive complex” has been determined to 2.4-Å resolution by X-ray crystallography (PDB 3MW9). RESULTS
155 176 X-ray crystallography experimental_method When GDH is bound to NADH, GTP, and glutamate, the enzyme adopts a closed conformation; this “abortive complex” has been determined to 2.4-Å resolution by X-ray crystallography (PDB 3MW9). RESULTS
9 27 crystal structures evidence However, crystal structures of GDH bound only to NADH or to GTP have not yet been reported. RESULTS
31 34 GDH protein However, crystal structures of GDH bound only to NADH or to GTP have not yet been reported. RESULTS
35 48 bound only to protein_state However, crystal structures of GDH bound only to NADH or to GTP have not yet been reported. RESULTS
49 53 NADH chemical However, crystal structures of GDH bound only to NADH or to GTP have not yet been reported. RESULTS
57 59 to protein_state However, crystal structures of GDH bound only to NADH or to GTP have not yet been reported. RESULTS
60 63 GTP chemical However, crystal structures of GDH bound only to NADH or to GTP have not yet been reported. RESULTS
22 26 NADH chemical To test the effect of NADH binding on GDH conformation in solution, we determined the structure of this binary complex using cryo-EM methods combined with three-dimensional classification. RESULTS
38 41 GDH protein To test the effect of NADH binding on GDH conformation in solution, we determined the structure of this binary complex using cryo-EM methods combined with three-dimensional classification. RESULTS
86 95 structure evidence To test the effect of NADH binding on GDH conformation in solution, we determined the structure of this binary complex using cryo-EM methods combined with three-dimensional classification. RESULTS
125 132 cryo-EM experimental_method To test the effect of NADH binding on GDH conformation in solution, we determined the structure of this binary complex using cryo-EM methods combined with three-dimensional classification. RESULTS
155 187 three-dimensional classification experimental_method To test the effect of NADH binding on GDH conformation in solution, we determined the structure of this binary complex using cryo-EM methods combined with three-dimensional classification. RESULTS
46 50 open protein_state Two dominant conformational states, in an all open or all closed conformation were detected, segregated (Fig. 2D), and further refined to near-atomic resolution (∼3.3 Å; Supplemental Fig. 2). RESULTS
58 64 closed protein_state Two dominant conformational states, in an all open or all closed conformation were detected, segregated (Fig. 2D), and further refined to near-atomic resolution (∼3.3 Å; Supplemental Fig. 2). RESULTS
0 9 Densities evidence Densities for 12 molecules of bound NADH were identified in maps of both open and closed states (Supplemental Fig. 4). RESULTS
30 35 bound protein_state Densities for 12 molecules of bound NADH were identified in maps of both open and closed states (Supplemental Fig. 4). RESULTS
36 40 NADH chemical Densities for 12 molecules of bound NADH were identified in maps of both open and closed states (Supplemental Fig. 4). RESULTS
60 64 maps evidence Densities for 12 molecules of bound NADH were identified in maps of both open and closed states (Supplemental Fig. 4). RESULTS
73 77 open protein_state Densities for 12 molecules of bound NADH were identified in maps of both open and closed states (Supplemental Fig. 4). RESULTS
82 88 closed protein_state Densities for 12 molecules of bound NADH were identified in maps of both open and closed states (Supplemental Fig. 4). RESULTS
4 14 NADH-bound protein_state The NADH-bound closed conformation matches the structure of the quaternary complex observed by X-ray crystallography, with the exception that density corresponding to GTP and glutamate was absent in the cryo-EM-derived map. RESULTS
15 21 closed protein_state The NADH-bound closed conformation matches the structure of the quaternary complex observed by X-ray crystallography, with the exception that density corresponding to GTP and glutamate was absent in the cryo-EM-derived map. RESULTS
47 56 structure evidence The NADH-bound closed conformation matches the structure of the quaternary complex observed by X-ray crystallography, with the exception that density corresponding to GTP and glutamate was absent in the cryo-EM-derived map. RESULTS
95 116 X-ray crystallography experimental_method The NADH-bound closed conformation matches the structure of the quaternary complex observed by X-ray crystallography, with the exception that density corresponding to GTP and glutamate was absent in the cryo-EM-derived map. RESULTS
142 149 density evidence The NADH-bound closed conformation matches the structure of the quaternary complex observed by X-ray crystallography, with the exception that density corresponding to GTP and glutamate was absent in the cryo-EM-derived map. RESULTS
167 170 GTP chemical The NADH-bound closed conformation matches the structure of the quaternary complex observed by X-ray crystallography, with the exception that density corresponding to GTP and glutamate was absent in the cryo-EM-derived map. RESULTS
175 184 glutamate chemical The NADH-bound closed conformation matches the structure of the quaternary complex observed by X-ray crystallography, with the exception that density corresponding to GTP and glutamate was absent in the cryo-EM-derived map. RESULTS
203 210 cryo-EM experimental_method The NADH-bound closed conformation matches the structure of the quaternary complex observed by X-ray crystallography, with the exception that density corresponding to GTP and glutamate was absent in the cryo-EM-derived map. RESULTS
219 222 map evidence The NADH-bound closed conformation matches the structure of the quaternary complex observed by X-ray crystallography, with the exception that density corresponding to GTP and glutamate was absent in the cryo-EM-derived map. RESULTS
18 28 NADH-bound protein_state Comparison of the NADH-bound closed conformation to the NADH-bound open conformation shows that, as expected, the catalytic cleft is closed and the NBDs are displaced toward the equatorial plane, accompanied by a rotation of the pivot helix by ∼7°, concomitant with a large conformational change in the antennae domains (Figs. 1 and 2D). RESULTS
29 35 closed protein_state Comparison of the NADH-bound closed conformation to the NADH-bound open conformation shows that, as expected, the catalytic cleft is closed and the NBDs are displaced toward the equatorial plane, accompanied by a rotation of the pivot helix by ∼7°, concomitant with a large conformational change in the antennae domains (Figs. 1 and 2D). RESULTS
56 66 NADH-bound protein_state Comparison of the NADH-bound closed conformation to the NADH-bound open conformation shows that, as expected, the catalytic cleft is closed and the NBDs are displaced toward the equatorial plane, accompanied by a rotation of the pivot helix by ∼7°, concomitant with a large conformational change in the antennae domains (Figs. 1 and 2D). RESULTS
67 71 open protein_state Comparison of the NADH-bound closed conformation to the NADH-bound open conformation shows that, as expected, the catalytic cleft is closed and the NBDs are displaced toward the equatorial plane, accompanied by a rotation of the pivot helix by ∼7°, concomitant with a large conformational change in the antennae domains (Figs. 1 and 2D). RESULTS
114 129 catalytic cleft site Comparison of the NADH-bound closed conformation to the NADH-bound open conformation shows that, as expected, the catalytic cleft is closed and the NBDs are displaced toward the equatorial plane, accompanied by a rotation of the pivot helix by ∼7°, concomitant with a large conformational change in the antennae domains (Figs. 1 and 2D). RESULTS
133 139 closed protein_state Comparison of the NADH-bound closed conformation to the NADH-bound open conformation shows that, as expected, the catalytic cleft is closed and the NBDs are displaced toward the equatorial plane, accompanied by a rotation of the pivot helix by ∼7°, concomitant with a large conformational change in the antennae domains (Figs. 1 and 2D). RESULTS
148 152 NBDs structure_element Comparison of the NADH-bound closed conformation to the NADH-bound open conformation shows that, as expected, the catalytic cleft is closed and the NBDs are displaced toward the equatorial plane, accompanied by a rotation of the pivot helix by ∼7°, concomitant with a large conformational change in the antennae domains (Figs. 1 and 2D). RESULTS
229 240 pivot helix structure_element Comparison of the NADH-bound closed conformation to the NADH-bound open conformation shows that, as expected, the catalytic cleft is closed and the NBDs are displaced toward the equatorial plane, accompanied by a rotation of the pivot helix by ∼7°, concomitant with a large conformational change in the antennae domains (Figs. 1 and 2D). RESULTS
303 311 antennae structure_element Comparison of the NADH-bound closed conformation to the NADH-bound open conformation shows that, as expected, the catalytic cleft is closed and the NBDs are displaced toward the equatorial plane, accompanied by a rotation of the pivot helix by ∼7°, concomitant with a large conformational change in the antennae domains (Figs. 1 and 2D). RESULTS
21 31 NADH-bound protein_state A comparison between NADH-bound open and closed conformations also involves a displacement of helix 5 (residues 171–186), as well as a tilt of the core β-sheets relative to the equatorial plane of the enzyme (residues 57–97, 122–130) and α-helix 2 (residues 36–54), and a bending of the N-terminal helix. RESULTS
32 36 open protein_state A comparison between NADH-bound open and closed conformations also involves a displacement of helix 5 (residues 171–186), as well as a tilt of the core β-sheets relative to the equatorial plane of the enzyme (residues 57–97, 122–130) and α-helix 2 (residues 36–54), and a bending of the N-terminal helix. RESULTS
41 47 closed protein_state A comparison between NADH-bound open and closed conformations also involves a displacement of helix 5 (residues 171–186), as well as a tilt of the core β-sheets relative to the equatorial plane of the enzyme (residues 57–97, 122–130) and α-helix 2 (residues 36–54), and a bending of the N-terminal helix. RESULTS
94 101 helix 5 structure_element A comparison between NADH-bound open and closed conformations also involves a displacement of helix 5 (residues 171–186), as well as a tilt of the core β-sheets relative to the equatorial plane of the enzyme (residues 57–97, 122–130) and α-helix 2 (residues 36–54), and a bending of the N-terminal helix. RESULTS
112 119 171–186 residue_range A comparison between NADH-bound open and closed conformations also involves a displacement of helix 5 (residues 171–186), as well as a tilt of the core β-sheets relative to the equatorial plane of the enzyme (residues 57–97, 122–130) and α-helix 2 (residues 36–54), and a bending of the N-terminal helix. RESULTS
152 160 β-sheets structure_element A comparison between NADH-bound open and closed conformations also involves a displacement of helix 5 (residues 171–186), as well as a tilt of the core β-sheets relative to the equatorial plane of the enzyme (residues 57–97, 122–130) and α-helix 2 (residues 36–54), and a bending of the N-terminal helix. RESULTS
218 223 57–97 residue_range A comparison between NADH-bound open and closed conformations also involves a displacement of helix 5 (residues 171–186), as well as a tilt of the core β-sheets relative to the equatorial plane of the enzyme (residues 57–97, 122–130) and α-helix 2 (residues 36–54), and a bending of the N-terminal helix. RESULTS
225 232 122–130 residue_range A comparison between NADH-bound open and closed conformations also involves a displacement of helix 5 (residues 171–186), as well as a tilt of the core β-sheets relative to the equatorial plane of the enzyme (residues 57–97, 122–130) and α-helix 2 (residues 36–54), and a bending of the N-terminal helix. RESULTS
238 247 α-helix 2 structure_element A comparison between NADH-bound open and closed conformations also involves a displacement of helix 5 (residues 171–186), as well as a tilt of the core β-sheets relative to the equatorial plane of the enzyme (residues 57–97, 122–130) and α-helix 2 (residues 36–54), and a bending of the N-terminal helix. RESULTS
258 263 36–54 residue_range A comparison between NADH-bound open and closed conformations also involves a displacement of helix 5 (residues 171–186), as well as a tilt of the core β-sheets relative to the equatorial plane of the enzyme (residues 57–97, 122–130) and α-helix 2 (residues 36–54), and a bending of the N-terminal helix. RESULTS
298 303 helix structure_element A comparison between NADH-bound open and closed conformations also involves a displacement of helix 5 (residues 171–186), as well as a tilt of the core β-sheets relative to the equatorial plane of the enzyme (residues 57–97, 122–130) and α-helix 2 (residues 36–54), and a bending of the N-terminal helix. RESULTS
21 36 catalytic cleft site Thus, closure of the catalytic cleft is accompanied by a quaternary structural change that can be described as a global bending of the structure about an axis that runs parallel to the pivot helix, accompanied by an expansion of the core (Figs. 1A and 2D). RESULTS
135 144 structure evidence Thus, closure of the catalytic cleft is accompanied by a quaternary structural change that can be described as a global bending of the structure about an axis that runs parallel to the pivot helix, accompanied by an expansion of the core (Figs. 1A and 2D). RESULTS
185 196 pivot helix structure_element Thus, closure of the catalytic cleft is accompanied by a quaternary structural change that can be described as a global bending of the structure about an axis that runs parallel to the pivot helix, accompanied by an expansion of the core (Figs. 1A and 2D). RESULTS
25 33 GDH/NADH complex_assembly Detailed analysis of the GDH/NADH structures shows that both the adenosine and nicotinamide moieties of NADH bind to the catalytic site within the NBD in nearly the same orientation in both the open and the closed states, and display closely comparable interactions with the Rossmann fold (Fig. 3, A and B). RESULTS
34 44 structures evidence Detailed analysis of the GDH/NADH structures shows that both the adenosine and nicotinamide moieties of NADH bind to the catalytic site within the NBD in nearly the same orientation in both the open and the closed states, and display closely comparable interactions with the Rossmann fold (Fig. 3, A and B). RESULTS
104 108 NADH chemical Detailed analysis of the GDH/NADH structures shows that both the adenosine and nicotinamide moieties of NADH bind to the catalytic site within the NBD in nearly the same orientation in both the open and the closed states, and display closely comparable interactions with the Rossmann fold (Fig. 3, A and B). RESULTS
121 135 catalytic site site Detailed analysis of the GDH/NADH structures shows that both the adenosine and nicotinamide moieties of NADH bind to the catalytic site within the NBD in nearly the same orientation in both the open and the closed states, and display closely comparable interactions with the Rossmann fold (Fig. 3, A and B). RESULTS
147 150 NBD structure_element Detailed analysis of the GDH/NADH structures shows that both the adenosine and nicotinamide moieties of NADH bind to the catalytic site within the NBD in nearly the same orientation in both the open and the closed states, and display closely comparable interactions with the Rossmann fold (Fig. 3, A and B). RESULTS
194 198 open protein_state Detailed analysis of the GDH/NADH structures shows that both the adenosine and nicotinamide moieties of NADH bind to the catalytic site within the NBD in nearly the same orientation in both the open and the closed states, and display closely comparable interactions with the Rossmann fold (Fig. 3, A and B). RESULTS
207 213 closed protein_state Detailed analysis of the GDH/NADH structures shows that both the adenosine and nicotinamide moieties of NADH bind to the catalytic site within the NBD in nearly the same orientation in both the open and the closed states, and display closely comparable interactions with the Rossmann fold (Fig. 3, A and B). RESULTS
275 288 Rossmann fold structure_element Detailed analysis of the GDH/NADH structures shows that both the adenosine and nicotinamide moieties of NADH bind to the catalytic site within the NBD in nearly the same orientation in both the open and the closed states, and display closely comparable interactions with the Rossmann fold (Fig. 3, A and B). RESULTS
7 22 regulatory site site At the regulatory site, where either ADP can bind as an activator or NADH can bind as an inhibitor, the binding of the adenine moiety of NADH is nearly identical between the two conformers. RESULTS
37 40 ADP chemical At the regulatory site, where either ADP can bind as an activator or NADH can bind as an inhibitor, the binding of the adenine moiety of NADH is nearly identical between the two conformers. RESULTS
69 73 NADH chemical At the regulatory site, where either ADP can bind as an activator or NADH can bind as an inhibitor, the binding of the adenine moiety of NADH is nearly identical between the two conformers. RESULTS
137 141 NADH chemical At the regulatory site, where either ADP can bind as an activator or NADH can bind as an inhibitor, the binding of the adenine moiety of NADH is nearly identical between the two conformers. RESULTS
7 13 closed protein_state In the closed state, the nicotinamide group is oriented toward the center of the hexamer, inserted into a narrow cavity between two adjacent subunits in the trimer. RESULTS
81 88 hexamer oligomeric_state In the closed state, the nicotinamide group is oriented toward the center of the hexamer, inserted into a narrow cavity between two adjacent subunits in the trimer. RESULTS
113 119 cavity site In the closed state, the nicotinamide group is oriented toward the center of the hexamer, inserted into a narrow cavity between two adjacent subunits in the trimer. RESULTS
141 149 subunits structure_element In the closed state, the nicotinamide group is oriented toward the center of the hexamer, inserted into a narrow cavity between two adjacent subunits in the trimer. RESULTS
157 163 trimer oligomeric_state In the closed state, the nicotinamide group is oriented toward the center of the hexamer, inserted into a narrow cavity between two adjacent subunits in the trimer. RESULTS
41 45 NADH chemical There are extensive interactions between NADH and the residues lining this cavity, which may explain the well-defined density of this portion of NADH in the closed state. RESULTS
75 81 cavity site There are extensive interactions between NADH and the residues lining this cavity, which may explain the well-defined density of this portion of NADH in the closed state. RESULTS
118 125 density evidence There are extensive interactions between NADH and the residues lining this cavity, which may explain the well-defined density of this portion of NADH in the closed state. RESULTS
145 149 NADH chemical There are extensive interactions between NADH and the residues lining this cavity, which may explain the well-defined density of this portion of NADH in the closed state. RESULTS
157 163 closed protein_state There are extensive interactions between NADH and the residues lining this cavity, which may explain the well-defined density of this portion of NADH in the closed state. RESULTS
20 24 open protein_state In contrast, in the open conformation, the cavity present in the closed state becomes too narrow for the nicotinamide group; instead, the group is oriented in the opposite direction, parallel to the pivot helix with the amido group extending toward the C-terminal end of the helix. RESULTS
43 49 cavity site In contrast, in the open conformation, the cavity present in the closed state becomes too narrow for the nicotinamide group; instead, the group is oriented in the opposite direction, parallel to the pivot helix with the amido group extending toward the C-terminal end of the helix. RESULTS
65 71 closed protein_state In contrast, in the open conformation, the cavity present in the closed state becomes too narrow for the nicotinamide group; instead, the group is oriented in the opposite direction, parallel to the pivot helix with the amido group extending toward the C-terminal end of the helix. RESULTS
199 210 pivot helix structure_element In contrast, in the open conformation, the cavity present in the closed state becomes too narrow for the nicotinamide group; instead, the group is oriented in the opposite direction, parallel to the pivot helix with the amido group extending toward the C-terminal end of the helix. RESULTS
275 280 helix structure_element In contrast, in the open conformation, the cavity present in the closed state becomes too narrow for the nicotinamide group; instead, the group is oriented in the opposite direction, parallel to the pivot helix with the amido group extending toward the C-terminal end of the helix. RESULTS
17 21 NADH chemical Detailed view of NADH conformation in catalytic and regulatory sites. (A, B) NADH density (purple) and interactions in the catalytic sites of closed (A) and open (B) states. (C, D) NADH density (red) and interactions in the regulatory sites of closed (C) and open (D) states. FIG
38 68 catalytic and regulatory sites site Detailed view of NADH conformation in catalytic and regulatory sites. (A, B) NADH density (purple) and interactions in the catalytic sites of closed (A) and open (B) states. (C, D) NADH density (red) and interactions in the regulatory sites of closed (C) and open (D) states. FIG
77 81 NADH chemical Detailed view of NADH conformation in catalytic and regulatory sites. (A, B) NADH density (purple) and interactions in the catalytic sites of closed (A) and open (B) states. (C, D) NADH density (red) and interactions in the regulatory sites of closed (C) and open (D) states. FIG
82 89 density evidence Detailed view of NADH conformation in catalytic and regulatory sites. (A, B) NADH density (purple) and interactions in the catalytic sites of closed (A) and open (B) states. (C, D) NADH density (red) and interactions in the regulatory sites of closed (C) and open (D) states. FIG
123 138 catalytic sites site Detailed view of NADH conformation in catalytic and regulatory sites. (A, B) NADH density (purple) and interactions in the catalytic sites of closed (A) and open (B) states. (C, D) NADH density (red) and interactions in the regulatory sites of closed (C) and open (D) states. FIG
142 148 closed protein_state Detailed view of NADH conformation in catalytic and regulatory sites. (A, B) NADH density (purple) and interactions in the catalytic sites of closed (A) and open (B) states. (C, D) NADH density (red) and interactions in the regulatory sites of closed (C) and open (D) states. FIG
157 161 open protein_state Detailed view of NADH conformation in catalytic and regulatory sites. (A, B) NADH density (purple) and interactions in the catalytic sites of closed (A) and open (B) states. (C, D) NADH density (red) and interactions in the regulatory sites of closed (C) and open (D) states. FIG
181 185 NADH chemical Detailed view of NADH conformation in catalytic and regulatory sites. (A, B) NADH density (purple) and interactions in the catalytic sites of closed (A) and open (B) states. (C, D) NADH density (red) and interactions in the regulatory sites of closed (C) and open (D) states. FIG
186 193 density evidence Detailed view of NADH conformation in catalytic and regulatory sites. (A, B) NADH density (purple) and interactions in the catalytic sites of closed (A) and open (B) states. (C, D) NADH density (red) and interactions in the regulatory sites of closed (C) and open (D) states. FIG
224 240 regulatory sites site Detailed view of NADH conformation in catalytic and regulatory sites. (A, B) NADH density (purple) and interactions in the catalytic sites of closed (A) and open (B) states. (C, D) NADH density (red) and interactions in the regulatory sites of closed (C) and open (D) states. FIG
244 250 closed protein_state Detailed view of NADH conformation in catalytic and regulatory sites. (A, B) NADH density (purple) and interactions in the catalytic sites of closed (A) and open (B) states. (C, D) NADH density (red) and interactions in the regulatory sites of closed (C) and open (D) states. FIG
259 263 open protein_state Detailed view of NADH conformation in catalytic and regulatory sites. (A, B) NADH density (purple) and interactions in the catalytic sites of closed (A) and open (B) states. (C, D) NADH density (red) and interactions in the regulatory sites of closed (C) and open (D) states. FIG
85 91 closed protein_state Although there is a difference in orientation of the nicotinamide moiety between the closed and open states in the regulatory site, in both structures the adenine portion of NADH has a similar binding pocket and is located in almost exactly the same position as ADP, a potent activator of GDH function (Supplemental Fig. 5). RESULTS
96 100 open protein_state Although there is a difference in orientation of the nicotinamide moiety between the closed and open states in the regulatory site, in both structures the adenine portion of NADH has a similar binding pocket and is located in almost exactly the same position as ADP, a potent activator of GDH function (Supplemental Fig. 5). RESULTS
115 130 regulatory site site Although there is a difference in orientation of the nicotinamide moiety between the closed and open states in the regulatory site, in both structures the adenine portion of NADH has a similar binding pocket and is located in almost exactly the same position as ADP, a potent activator of GDH function (Supplemental Fig. 5). RESULTS
140 150 structures evidence Although there is a difference in orientation of the nicotinamide moiety between the closed and open states in the regulatory site, in both structures the adenine portion of NADH has a similar binding pocket and is located in almost exactly the same position as ADP, a potent activator of GDH function (Supplemental Fig. 5). RESULTS
174 178 NADH chemical Although there is a difference in orientation of the nicotinamide moiety between the closed and open states in the regulatory site, in both structures the adenine portion of NADH has a similar binding pocket and is located in almost exactly the same position as ADP, a potent activator of GDH function (Supplemental Fig. 5). RESULTS
193 207 binding pocket site Although there is a difference in orientation of the nicotinamide moiety between the closed and open states in the regulatory site, in both structures the adenine portion of NADH has a similar binding pocket and is located in almost exactly the same position as ADP, a potent activator of GDH function (Supplemental Fig. 5). RESULTS
262 265 ADP chemical Although there is a difference in orientation of the nicotinamide moiety between the closed and open states in the regulatory site, in both structures the adenine portion of NADH has a similar binding pocket and is located in almost exactly the same position as ADP, a potent activator of GDH function (Supplemental Fig. 5). RESULTS
289 292 GDH protein Although there is a difference in orientation of the nicotinamide moiety between the closed and open states in the regulatory site, in both structures the adenine portion of NADH has a similar binding pocket and is located in almost exactly the same position as ADP, a potent activator of GDH function (Supplemental Fig. 5). RESULTS
7 11 open protein_state In the open state, the binding of ADP or NADH is further stabilized by His209, a residue that undergoes a large movement during the transition from open to closed conformation (Fig. 3, C and D). RESULTS
34 37 ADP chemical In the open state, the binding of ADP or NADH is further stabilized by His209, a residue that undergoes a large movement during the transition from open to closed conformation (Fig. 3, C and D). RESULTS
41 45 NADH chemical In the open state, the binding of ADP or NADH is further stabilized by His209, a residue that undergoes a large movement during the transition from open to closed conformation (Fig. 3, C and D). RESULTS
71 77 His209 residue_name_number In the open state, the binding of ADP or NADH is further stabilized by His209, a residue that undergoes a large movement during the transition from open to closed conformation (Fig. 3, C and D). RESULTS
148 152 open protein_state In the open state, the binding of ADP or NADH is further stabilized by His209, a residue that undergoes a large movement during the transition from open to closed conformation (Fig. 3, C and D). RESULTS
156 162 closed protein_state In the open state, the binding of ADP or NADH is further stabilized by His209, a residue that undergoes a large movement during the transition from open to closed conformation (Fig. 3, C and D). RESULTS
7 11 open protein_state In the open conformation, the distance between His209 and the α-phosphate of NADH is ∼4.4 Å, which is comparable with the corresponding distance in the ADP-bound conformation. RESULTS
47 53 His209 residue_name_number In the open conformation, the distance between His209 and the α-phosphate of NADH is ∼4.4 Å, which is comparable with the corresponding distance in the ADP-bound conformation. RESULTS
77 81 NADH chemical In the open conformation, the distance between His209 and the α-phosphate of NADH is ∼4.4 Å, which is comparable with the corresponding distance in the ADP-bound conformation. RESULTS
152 161 ADP-bound protein_state In the open conformation, the distance between His209 and the α-phosphate of NADH is ∼4.4 Å, which is comparable with the corresponding distance in the ADP-bound conformation. RESULTS
7 13 closed protein_state In the closed conformation, however, this key histidine residue is >10.5 Å away from the nearest phosphate group on NADH, altering a critical stabilization point within the regulatory site. RESULTS
46 55 histidine residue_name In the closed conformation, however, this key histidine residue is >10.5 Å away from the nearest phosphate group on NADH, altering a critical stabilization point within the regulatory site. RESULTS
116 120 NADH chemical In the closed conformation, however, this key histidine residue is >10.5 Å away from the nearest phosphate group on NADH, altering a critical stabilization point within the regulatory site. RESULTS
173 188 regulatory site site In the closed conformation, however, this key histidine residue is >10.5 Å away from the nearest phosphate group on NADH, altering a critical stabilization point within the regulatory site. RESULTS
48 52 NADH chemical This suggests that although the conformation of NADH in the open state regulatory site more closely mimics the binding of ADP, the conformation of NADH in the closed state regulatory site is significantly different; these differences may contribute to the opposite effects of NADH and ADP on GDH enzymatic activity. RESULTS
60 64 open protein_state This suggests that although the conformation of NADH in the open state regulatory site more closely mimics the binding of ADP, the conformation of NADH in the closed state regulatory site is significantly different; these differences may contribute to the opposite effects of NADH and ADP on GDH enzymatic activity. RESULTS
71 86 regulatory site site This suggests that although the conformation of NADH in the open state regulatory site more closely mimics the binding of ADP, the conformation of NADH in the closed state regulatory site is significantly different; these differences may contribute to the opposite effects of NADH and ADP on GDH enzymatic activity. RESULTS
122 125 ADP chemical This suggests that although the conformation of NADH in the open state regulatory site more closely mimics the binding of ADP, the conformation of NADH in the closed state regulatory site is significantly different; these differences may contribute to the opposite effects of NADH and ADP on GDH enzymatic activity. RESULTS
147 151 NADH chemical This suggests that although the conformation of NADH in the open state regulatory site more closely mimics the binding of ADP, the conformation of NADH in the closed state regulatory site is significantly different; these differences may contribute to the opposite effects of NADH and ADP on GDH enzymatic activity. RESULTS
159 165 closed protein_state This suggests that although the conformation of NADH in the open state regulatory site more closely mimics the binding of ADP, the conformation of NADH in the closed state regulatory site is significantly different; these differences may contribute to the opposite effects of NADH and ADP on GDH enzymatic activity. RESULTS
172 187 regulatory site site This suggests that although the conformation of NADH in the open state regulatory site more closely mimics the binding of ADP, the conformation of NADH in the closed state regulatory site is significantly different; these differences may contribute to the opposite effects of NADH and ADP on GDH enzymatic activity. RESULTS
276 280 NADH chemical This suggests that although the conformation of NADH in the open state regulatory site more closely mimics the binding of ADP, the conformation of NADH in the closed state regulatory site is significantly different; these differences may contribute to the opposite effects of NADH and ADP on GDH enzymatic activity. RESULTS
285 288 ADP chemical This suggests that although the conformation of NADH in the open state regulatory site more closely mimics the binding of ADP, the conformation of NADH in the closed state regulatory site is significantly different; these differences may contribute to the opposite effects of NADH and ADP on GDH enzymatic activity. RESULTS
292 295 GDH protein This suggests that although the conformation of NADH in the open state regulatory site more closely mimics the binding of ADP, the conformation of NADH in the closed state regulatory site is significantly different; these differences may contribute to the opposite effects of NADH and ADP on GDH enzymatic activity. RESULTS
7 17 absence of protein_state In the absence of NADH, GTP binds weakly to GDH with a dissociation constant of ∼20 μM. Cryo-EM analysis of GDH incubated with GTP resulted in a structure at an overall resolution of 3.5 Å, showing that it is in an open conformation (Supplemental Fig. 6), with all NBDs in the open state. RESULTS
18 22 NADH chemical In the absence of NADH, GTP binds weakly to GDH with a dissociation constant of ∼20 μM. Cryo-EM analysis of GDH incubated with GTP resulted in a structure at an overall resolution of 3.5 Å, showing that it is in an open conformation (Supplemental Fig. 6), with all NBDs in the open state. RESULTS
24 27 GTP chemical In the absence of NADH, GTP binds weakly to GDH with a dissociation constant of ∼20 μM. Cryo-EM analysis of GDH incubated with GTP resulted in a structure at an overall resolution of 3.5 Å, showing that it is in an open conformation (Supplemental Fig. 6), with all NBDs in the open state. RESULTS
44 47 GDH protein In the absence of NADH, GTP binds weakly to GDH with a dissociation constant of ∼20 μM. Cryo-EM analysis of GDH incubated with GTP resulted in a structure at an overall resolution of 3.5 Å, showing that it is in an open conformation (Supplemental Fig. 6), with all NBDs in the open state. RESULTS
55 76 dissociation constant evidence In the absence of NADH, GTP binds weakly to GDH with a dissociation constant of ∼20 μM. Cryo-EM analysis of GDH incubated with GTP resulted in a structure at an overall resolution of 3.5 Å, showing that it is in an open conformation (Supplemental Fig. 6), with all NBDs in the open state. RESULTS
88 95 Cryo-EM experimental_method In the absence of NADH, GTP binds weakly to GDH with a dissociation constant of ∼20 μM. Cryo-EM analysis of GDH incubated with GTP resulted in a structure at an overall resolution of 3.5 Å, showing that it is in an open conformation (Supplemental Fig. 6), with all NBDs in the open state. RESULTS
108 111 GDH protein In the absence of NADH, GTP binds weakly to GDH with a dissociation constant of ∼20 μM. Cryo-EM analysis of GDH incubated with GTP resulted in a structure at an overall resolution of 3.5 Å, showing that it is in an open conformation (Supplemental Fig. 6), with all NBDs in the open state. RESULTS
112 126 incubated with protein_state In the absence of NADH, GTP binds weakly to GDH with a dissociation constant of ∼20 μM. Cryo-EM analysis of GDH incubated with GTP resulted in a structure at an overall resolution of 3.5 Å, showing that it is in an open conformation (Supplemental Fig. 6), with all NBDs in the open state. RESULTS
127 130 GTP chemical In the absence of NADH, GTP binds weakly to GDH with a dissociation constant of ∼20 μM. Cryo-EM analysis of GDH incubated with GTP resulted in a structure at an overall resolution of 3.5 Å, showing that it is in an open conformation (Supplemental Fig. 6), with all NBDs in the open state. RESULTS
145 154 structure evidence In the absence of NADH, GTP binds weakly to GDH with a dissociation constant of ∼20 μM. Cryo-EM analysis of GDH incubated with GTP resulted in a structure at an overall resolution of 3.5 Å, showing that it is in an open conformation (Supplemental Fig. 6), with all NBDs in the open state. RESULTS
215 219 open protein_state In the absence of NADH, GTP binds weakly to GDH with a dissociation constant of ∼20 μM. Cryo-EM analysis of GDH incubated with GTP resulted in a structure at an overall resolution of 3.5 Å, showing that it is in an open conformation (Supplemental Fig. 6), with all NBDs in the open state. RESULTS
265 269 NBDs structure_element In the absence of NADH, GTP binds weakly to GDH with a dissociation constant of ∼20 μM. Cryo-EM analysis of GDH incubated with GTP resulted in a structure at an overall resolution of 3.5 Å, showing that it is in an open conformation (Supplemental Fig. 6), with all NBDs in the open state. RESULTS
277 281 open protein_state In the absence of NADH, GTP binds weakly to GDH with a dissociation constant of ∼20 μM. Cryo-EM analysis of GDH incubated with GTP resulted in a structure at an overall resolution of 3.5 Å, showing that it is in an open conformation (Supplemental Fig. 6), with all NBDs in the open state. RESULTS
4 11 density evidence The density for GTP is not very well defined, suggesting considerable wobble in the binding site. RESULTS
16 19 GTP chemical The density for GTP is not very well defined, suggesting considerable wobble in the binding site. RESULTS
84 96 binding site site The density for GTP is not very well defined, suggesting considerable wobble in the binding site. RESULTS
0 11 Subtraction experimental_method Subtraction of the GTP-bound map with that of the apo state shows that GTP binding can nevertheless be visualized specifically in the GTP binding site (Supplemental Fig. 6). RESULTS
19 28 GTP-bound protein_state Subtraction of the GTP-bound map with that of the apo state shows that GTP binding can nevertheless be visualized specifically in the GTP binding site (Supplemental Fig. 6). RESULTS
29 32 map evidence Subtraction of the GTP-bound map with that of the apo state shows that GTP binding can nevertheless be visualized specifically in the GTP binding site (Supplemental Fig. 6). RESULTS
50 53 apo protein_state Subtraction of the GTP-bound map with that of the apo state shows that GTP binding can nevertheless be visualized specifically in the GTP binding site (Supplemental Fig. 6). RESULTS
71 74 GTP chemical Subtraction of the GTP-bound map with that of the apo state shows that GTP binding can nevertheless be visualized specifically in the GTP binding site (Supplemental Fig. 6). RESULTS
134 150 GTP binding site site Subtraction of the GTP-bound map with that of the apo state shows that GTP binding can nevertheless be visualized specifically in the GTP binding site (Supplemental Fig. 6). RESULTS
28 31 GTP chemical Importantly, the binding of GTP alone does not appear to drive the transition from the open to the closed state of GDH. RESULTS
87 91 open protein_state Importantly, the binding of GTP alone does not appear to drive the transition from the open to the closed state of GDH. RESULTS
99 105 closed protein_state Importantly, the binding of GTP alone does not appear to drive the transition from the open to the closed state of GDH. RESULTS
115 118 GDH protein Importantly, the binding of GTP alone does not appear to drive the transition from the open to the closed state of GDH. RESULTS
32 36 NADH chemical To further dissect the roles of NADH and GTP in the transition from the open to closed conformations, we next determined structures of GDH in complex with both NADH and GTP, but without glutamate. RESULTS
41 44 GTP chemical To further dissect the roles of NADH and GTP in the transition from the open to closed conformations, we next determined structures of GDH in complex with both NADH and GTP, but without glutamate. RESULTS
72 76 open protein_state To further dissect the roles of NADH and GTP in the transition from the open to closed conformations, we next determined structures of GDH in complex with both NADH and GTP, but without glutamate. RESULTS
80 86 closed protein_state To further dissect the roles of NADH and GTP in the transition from the open to closed conformations, we next determined structures of GDH in complex with both NADH and GTP, but without glutamate. RESULTS
110 120 determined experimental_method To further dissect the roles of NADH and GTP in the transition from the open to closed conformations, we next determined structures of GDH in complex with both NADH and GTP, but without glutamate. RESULTS
121 131 structures evidence To further dissect the roles of NADH and GTP in the transition from the open to closed conformations, we next determined structures of GDH in complex with both NADH and GTP, but without glutamate. RESULTS
135 138 GDH protein To further dissect the roles of NADH and GTP in the transition from the open to closed conformations, we next determined structures of GDH in complex with both NADH and GTP, but without glutamate. RESULTS
139 154 in complex with protein_state To further dissect the roles of NADH and GTP in the transition from the open to closed conformations, we next determined structures of GDH in complex with both NADH and GTP, but without glutamate. RESULTS
160 164 NADH chemical To further dissect the roles of NADH and GTP in the transition from the open to closed conformations, we next determined structures of GDH in complex with both NADH and GTP, but without glutamate. RESULTS
169 172 GTP chemical To further dissect the roles of NADH and GTP in the transition from the open to closed conformations, we next determined structures of GDH in complex with both NADH and GTP, but without glutamate. RESULTS
178 185 without protein_state To further dissect the roles of NADH and GTP in the transition from the open to closed conformations, we next determined structures of GDH in complex with both NADH and GTP, but without glutamate. RESULTS
186 195 glutamate chemical To further dissect the roles of NADH and GTP in the transition from the open to closed conformations, we next determined structures of GDH in complex with both NADH and GTP, but without glutamate. RESULTS
5 9 NADH chemical When NADH and GTP are both present, classification reveals the presence of both closed and open GDH conformations, similar to the condition when only NADH is present (Fig. 4, A and B). RESULTS
14 17 GTP chemical When NADH and GTP are both present, classification reveals the presence of both closed and open GDH conformations, similar to the condition when only NADH is present (Fig. 4, A and B). RESULTS
36 50 classification experimental_method When NADH and GTP are both present, classification reveals the presence of both closed and open GDH conformations, similar to the condition when only NADH is present (Fig. 4, A and B). RESULTS
63 74 presence of protein_state When NADH and GTP are both present, classification reveals the presence of both closed and open GDH conformations, similar to the condition when only NADH is present (Fig. 4, A and B). RESULTS
80 86 closed protein_state When NADH and GTP are both present, classification reveals the presence of both closed and open GDH conformations, similar to the condition when only NADH is present (Fig. 4, A and B). RESULTS
91 95 open protein_state When NADH and GTP are both present, classification reveals the presence of both closed and open GDH conformations, similar to the condition when only NADH is present (Fig. 4, A and B). RESULTS
96 99 GDH protein When NADH and GTP are both present, classification reveals the presence of both closed and open GDH conformations, similar to the condition when only NADH is present (Fig. 4, A and B). RESULTS
150 154 NADH chemical When NADH and GTP are both present, classification reveals the presence of both closed and open GDH conformations, similar to the condition when only NADH is present (Fig. 4, A and B). RESULTS
0 37 Reconstruction without classification experimental_method Reconstruction without classification, however, yields a structure clearly in the closed conformation, suggesting that, in coordination with NADH, GTP may further stabilize the closed conformation. RESULTS
57 66 structure evidence Reconstruction without classification, however, yields a structure clearly in the closed conformation, suggesting that, in coordination with NADH, GTP may further stabilize the closed conformation. RESULTS
82 88 closed protein_state Reconstruction without classification, however, yields a structure clearly in the closed conformation, suggesting that, in coordination with NADH, GTP may further stabilize the closed conformation. RESULTS
141 145 NADH chemical Reconstruction without classification, however, yields a structure clearly in the closed conformation, suggesting that, in coordination with NADH, GTP may further stabilize the closed conformation. RESULTS
147 150 GTP chemical Reconstruction without classification, however, yields a structure clearly in the closed conformation, suggesting that, in coordination with NADH, GTP may further stabilize the closed conformation. RESULTS
177 183 closed protein_state Reconstruction without classification, however, yields a structure clearly in the closed conformation, suggesting that, in coordination with NADH, GTP may further stabilize the closed conformation. RESULTS
16 19 GTP chemical The location of GTP in the open and closed states of the GDH/NADH/GTP complex is similar to that in the crystal structure observed in the presence of NADH, GTP, and glutamate. RESULTS
27 31 open protein_state The location of GTP in the open and closed states of the GDH/NADH/GTP complex is similar to that in the crystal structure observed in the presence of NADH, GTP, and glutamate. RESULTS
36 42 closed protein_state The location of GTP in the open and closed states of the GDH/NADH/GTP complex is similar to that in the crystal structure observed in the presence of NADH, GTP, and glutamate. RESULTS
57 69 GDH/NADH/GTP complex_assembly The location of GTP in the open and closed states of the GDH/NADH/GTP complex is similar to that in the crystal structure observed in the presence of NADH, GTP, and glutamate. RESULTS
104 121 crystal structure evidence The location of GTP in the open and closed states of the GDH/NADH/GTP complex is similar to that in the crystal structure observed in the presence of NADH, GTP, and glutamate. RESULTS
138 149 presence of protein_state The location of GTP in the open and closed states of the GDH/NADH/GTP complex is similar to that in the crystal structure observed in the presence of NADH, GTP, and glutamate. RESULTS
150 154 NADH chemical The location of GTP in the open and closed states of the GDH/NADH/GTP complex is similar to that in the crystal structure observed in the presence of NADH, GTP, and glutamate. RESULTS
156 159 GTP chemical The location of GTP in the open and closed states of the GDH/NADH/GTP complex is similar to that in the crystal structure observed in the presence of NADH, GTP, and glutamate. RESULTS
165 174 glutamate chemical The location of GTP in the open and closed states of the GDH/NADH/GTP complex is similar to that in the crystal structure observed in the presence of NADH, GTP, and glutamate. RESULTS
26 30 NADH chemical Likewise, the position of NADH in the open and closed states closely resembles the position of NADH in the GDH/NADH open and closed structures. RESULTS
38 42 open protein_state Likewise, the position of NADH in the open and closed states closely resembles the position of NADH in the GDH/NADH open and closed structures. RESULTS
47 53 closed protein_state Likewise, the position of NADH in the open and closed states closely resembles the position of NADH in the GDH/NADH open and closed structures. RESULTS
95 99 NADH chemical Likewise, the position of NADH in the open and closed states closely resembles the position of NADH in the GDH/NADH open and closed structures. RESULTS
107 115 GDH/NADH complex_assembly Likewise, the position of NADH in the open and closed states closely resembles the position of NADH in the GDH/NADH open and closed structures. RESULTS
116 120 open protein_state Likewise, the position of NADH in the open and closed states closely resembles the position of NADH in the GDH/NADH open and closed structures. RESULTS
125 131 closed protein_state Likewise, the position of NADH in the open and closed states closely resembles the position of NADH in the GDH/NADH open and closed structures. RESULTS
132 142 structures evidence Likewise, the position of NADH in the open and closed states closely resembles the position of NADH in the GDH/NADH open and closed structures. RESULTS
31 35 open protein_state One key difference between the open and closed states of these structures is the position of the His209 residue: As mentioned above, His209 swings away from the adenine moiety of NADH in the closed state. RESULTS
40 46 closed protein_state One key difference between the open and closed states of these structures is the position of the His209 residue: As mentioned above, His209 swings away from the adenine moiety of NADH in the closed state. RESULTS
63 73 structures evidence One key difference between the open and closed states of these structures is the position of the His209 residue: As mentioned above, His209 swings away from the adenine moiety of NADH in the closed state. RESULTS
97 103 His209 residue_name_number One key difference between the open and closed states of these structures is the position of the His209 residue: As mentioned above, His209 swings away from the adenine moiety of NADH in the closed state. RESULTS
133 139 His209 residue_name_number One key difference between the open and closed states of these structures is the position of the His209 residue: As mentioned above, His209 swings away from the adenine moiety of NADH in the closed state. RESULTS
179 183 NADH chemical One key difference between the open and closed states of these structures is the position of the His209 residue: As mentioned above, His209 swings away from the adenine moiety of NADH in the closed state. RESULTS
191 197 closed protein_state One key difference between the open and closed states of these structures is the position of the His209 residue: As mentioned above, His209 swings away from the adenine moiety of NADH in the closed state. RESULTS
5 8 GTP chemical When GTP is present in the GTP binding site, His209 instead interacts with GTP, probably stabilizing the closed conformation (Fig. 4, C and D). RESULTS
27 43 GTP binding site site When GTP is present in the GTP binding site, His209 instead interacts with GTP, probably stabilizing the closed conformation (Fig. 4, C and D). RESULTS
45 51 His209 residue_name_number When GTP is present in the GTP binding site, His209 instead interacts with GTP, probably stabilizing the closed conformation (Fig. 4, C and D). RESULTS
75 78 GTP chemical When GTP is present in the GTP binding site, His209 instead interacts with GTP, probably stabilizing the closed conformation (Fig. 4, C and D). RESULTS
105 111 closed protein_state When GTP is present in the GTP binding site, His209 instead interacts with GTP, probably stabilizing the closed conformation (Fig. 4, C and D). RESULTS
6 9 GTP chemical Thus, GTP binding to GDH appears synergistic with NADH and displaces the conformational landscape toward the closed state. RESULTS
21 24 GDH protein Thus, GTP binding to GDH appears synergistic with NADH and displaces the conformational landscape toward the closed state. RESULTS
50 54 NADH chemical Thus, GTP binding to GDH appears synergistic with NADH and displaces the conformational landscape toward the closed state. RESULTS
109 115 closed protein_state Thus, GTP binding to GDH appears synergistic with NADH and displaces the conformational landscape toward the closed state. RESULTS
0 7 Cryo-EM experimental_method Cryo-EM structure of GDH bound to both NADH and GTP. FIG
8 17 structure evidence Cryo-EM structure of GDH bound to both NADH and GTP. FIG
21 24 GDH protein Cryo-EM structure of GDH bound to both NADH and GTP. FIG
25 33 bound to protein_state Cryo-EM structure of GDH bound to both NADH and GTP. FIG
39 43 NADH chemical Cryo-EM structure of GDH bound to both NADH and GTP. FIG
48 51 GTP chemical Cryo-EM structure of GDH bound to both NADH and GTP. FIG
34 38 open protein_state (A, B) Observation of co-existing open (A) and closed (B) conformations in the GDH-NADH-GTP ternary complex. FIG
47 53 closed protein_state (A, B) Observation of co-existing open (A) and closed (B) conformations in the GDH-NADH-GTP ternary complex. FIG
79 91 GDH-NADH-GTP complex_assembly (A, B) Observation of co-existing open (A) and closed (B) conformations in the GDH-NADH-GTP ternary complex. FIG
0 9 Densities evidence Densities for GTP (yellow) as well as NADH bound to both catalytic (purple) and regulatory (red) sites in each protomer are shown. FIG
14 17 GTP chemical Densities for GTP (yellow) as well as NADH bound to both catalytic (purple) and regulatory (red) sites in each protomer are shown. FIG
38 42 NADH chemical Densities for GTP (yellow) as well as NADH bound to both catalytic (purple) and regulatory (red) sites in each protomer are shown. FIG
43 51 bound to protein_state Densities for GTP (yellow) as well as NADH bound to both catalytic (purple) and regulatory (red) sites in each protomer are shown. FIG
57 66 catalytic site Densities for GTP (yellow) as well as NADH bound to both catalytic (purple) and regulatory (red) sites in each protomer are shown. FIG
80 90 regulatory site Densities for GTP (yellow) as well as NADH bound to both catalytic (purple) and regulatory (red) sites in each protomer are shown. FIG
97 102 sites site Densities for GTP (yellow) as well as NADH bound to both catalytic (purple) and regulatory (red) sites in each protomer are shown. FIG
111 119 protomer oligomeric_state Densities for GTP (yellow) as well as NADH bound to both catalytic (purple) and regulatory (red) sites in each protomer are shown. FIG
56 71 regulatory site site (C, D) Detailed inspection of the interactions near the regulatory site show that the orientation of His209 switches between the two states, which may allow interactions with bound GTP in the closed (D), but not open (C) conformation. FIG
101 107 His209 residue_name_number (C, D) Detailed inspection of the interactions near the regulatory site show that the orientation of His209 switches between the two states, which may allow interactions with bound GTP in the closed (D), but not open (C) conformation. FIG
175 180 bound protein_state (C, D) Detailed inspection of the interactions near the regulatory site show that the orientation of His209 switches between the two states, which may allow interactions with bound GTP in the closed (D), but not open (C) conformation. FIG
181 184 GTP chemical (C, D) Detailed inspection of the interactions near the regulatory site show that the orientation of His209 switches between the two states, which may allow interactions with bound GTP in the closed (D), but not open (C) conformation. FIG
192 198 closed protein_state (C, D) Detailed inspection of the interactions near the regulatory site show that the orientation of His209 switches between the two states, which may allow interactions with bound GTP in the closed (D), but not open (C) conformation. FIG
212 216 open protein_state (C, D) Detailed inspection of the interactions near the regulatory site show that the orientation of His209 switches between the two states, which may allow interactions with bound GTP in the closed (D), but not open (C) conformation. FIG
4 22 structural studies experimental_method Our structural studies thus establish that whether or not GTP is bound, NADH binding is detectable at catalytic and regulatory sites, in both the open and closed conformational states. RESULTS
58 61 GTP chemical Our structural studies thus establish that whether or not GTP is bound, NADH binding is detectable at catalytic and regulatory sites, in both the open and closed conformational states. RESULTS
65 70 bound protein_state Our structural studies thus establish that whether or not GTP is bound, NADH binding is detectable at catalytic and regulatory sites, in both the open and closed conformational states. RESULTS
72 76 NADH chemical Our structural studies thus establish that whether or not GTP is bound, NADH binding is detectable at catalytic and regulatory sites, in both the open and closed conformational states. RESULTS
102 132 catalytic and regulatory sites site Our structural studies thus establish that whether or not GTP is bound, NADH binding is detectable at catalytic and regulatory sites, in both the open and closed conformational states. RESULTS
146 150 open protein_state Our structural studies thus establish that whether or not GTP is bound, NADH binding is detectable at catalytic and regulatory sites, in both the open and closed conformational states. RESULTS
155 161 closed protein_state Our structural studies thus establish that whether or not GTP is bound, NADH binding is detectable at catalytic and regulatory sites, in both the open and closed conformational states. RESULTS
33 37 NADH chemical Whereas the orientation in which NADH binds at the catalytic site is similar for both conformations, the orientation of the nicotinamide portion of NADH in the regulatory site is different between the open and closed conformations (Figs. 3 and 4). RESULTS
51 65 catalytic site site Whereas the orientation in which NADH binds at the catalytic site is similar for both conformations, the orientation of the nicotinamide portion of NADH in the regulatory site is different between the open and closed conformations (Figs. 3 and 4). RESULTS
148 152 NADH chemical Whereas the orientation in which NADH binds at the catalytic site is similar for both conformations, the orientation of the nicotinamide portion of NADH in the regulatory site is different between the open and closed conformations (Figs. 3 and 4). RESULTS
160 175 regulatory site site Whereas the orientation in which NADH binds at the catalytic site is similar for both conformations, the orientation of the nicotinamide portion of NADH in the regulatory site is different between the open and closed conformations (Figs. 3 and 4). RESULTS
201 205 open protein_state Whereas the orientation in which NADH binds at the catalytic site is similar for both conformations, the orientation of the nicotinamide portion of NADH in the regulatory site is different between the open and closed conformations (Figs. 3 and 4). RESULTS
210 216 closed protein_state Whereas the orientation in which NADH binds at the catalytic site is similar for both conformations, the orientation of the nicotinamide portion of NADH in the regulatory site is different between the open and closed conformations (Figs. 3 and 4). RESULTS
7 13 closed protein_state In the closed state, the nicotinamide moiety is inserted into a well-defined cavity at the interface between two adjacent protomers in the trimer. RESULTS
77 83 cavity site In the closed state, the nicotinamide moiety is inserted into a well-defined cavity at the interface between two adjacent protomers in the trimer. RESULTS
91 100 interface site In the closed state, the nicotinamide moiety is inserted into a well-defined cavity at the interface between two adjacent protomers in the trimer. RESULTS
122 131 protomers oligomeric_state In the closed state, the nicotinamide moiety is inserted into a well-defined cavity at the interface between two adjacent protomers in the trimer. RESULTS
139 145 trimer oligomeric_state In the closed state, the nicotinamide moiety is inserted into a well-defined cavity at the interface between two adjacent protomers in the trimer. RESULTS
25 31 cavity site As mentioned above, this cavity is much narrower in the open state, suggesting that this cavity may be unavailable to the NADH nicotinamide moiety when the enzyme is in the open conformation. RESULTS
56 60 open protein_state As mentioned above, this cavity is much narrower in the open state, suggesting that this cavity may be unavailable to the NADH nicotinamide moiety when the enzyme is in the open conformation. RESULTS
89 95 cavity site As mentioned above, this cavity is much narrower in the open state, suggesting that this cavity may be unavailable to the NADH nicotinamide moiety when the enzyme is in the open conformation. RESULTS
122 126 NADH chemical As mentioned above, this cavity is much narrower in the open state, suggesting that this cavity may be unavailable to the NADH nicotinamide moiety when the enzyme is in the open conformation. RESULTS
173 177 open protein_state As mentioned above, this cavity is much narrower in the open state, suggesting that this cavity may be unavailable to the NADH nicotinamide moiety when the enzyme is in the open conformation. RESULTS
72 79 density evidence These structural features provide a potential explanation of the weaker density for the nicotinamide moiety of NADH in the open state, and may account for the higher reported affinity of NADH for the closed state. RESULTS
111 115 NADH chemical These structural features provide a potential explanation of the weaker density for the nicotinamide moiety of NADH in the open state, and may account for the higher reported affinity of NADH for the closed state. RESULTS
123 127 open protein_state These structural features provide a potential explanation of the weaker density for the nicotinamide moiety of NADH in the open state, and may account for the higher reported affinity of NADH for the closed state. RESULTS
187 191 NADH chemical These structural features provide a potential explanation of the weaker density for the nicotinamide moiety of NADH in the open state, and may account for the higher reported affinity of NADH for the closed state. RESULTS
200 206 closed protein_state These structural features provide a potential explanation of the weaker density for the nicotinamide moiety of NADH in the open state, and may account for the higher reported affinity of NADH for the closed state. RESULTS
93 97 open protein_state The role of the nicotinamide moiety in acting as a wedge that prevents the transition to the open conformation also suggests a structural explanation of the mechanism by which NADH binding inhibits the activity of the enzyme by stabilizing the closed conformation state. RESULTS
176 180 NADH chemical The role of the nicotinamide moiety in acting as a wedge that prevents the transition to the open conformation also suggests a structural explanation of the mechanism by which NADH binding inhibits the activity of the enzyme by stabilizing the closed conformation state. RESULTS
244 250 closed protein_state The role of the nicotinamide moiety in acting as a wedge that prevents the transition to the open conformation also suggests a structural explanation of the mechanism by which NADH binding inhibits the activity of the enzyme by stabilizing the closed conformation state. RESULTS
23 30 cryo-EM experimental_method The rapid emergence of cryo-EM as a tool for near-atomic resolution structure determination provides new opportunities for complementing atomic resolution information from X-ray crystallography, as illustrated here with GDH. RESULTS
68 91 structure determination experimental_method The rapid emergence of cryo-EM as a tool for near-atomic resolution structure determination provides new opportunities for complementing atomic resolution information from X-ray crystallography, as illustrated here with GDH. RESULTS
172 193 X-ray crystallography experimental_method The rapid emergence of cryo-EM as a tool for near-atomic resolution structure determination provides new opportunities for complementing atomic resolution information from X-ray crystallography, as illustrated here with GDH. RESULTS
220 223 GDH protein The rapid emergence of cryo-EM as a tool for near-atomic resolution structure determination provides new opportunities for complementing atomic resolution information from X-ray crystallography, as illustrated here with GDH. RESULTS
130 139 structure evidence Perhaps the most important contribution of these methods is the prospect that when there are discrete subpopulations present, the structure of each state can be determined at near-atomic resolution. What we demonstrate here with GDH is that by employing three-dimensional image classification approaches, we not only can isolate distinct, coexisting conformations, but we can also localize small molecule ligands in each of these conformations. RESULTS
229 232 GDH protein Perhaps the most important contribution of these methods is the prospect that when there are discrete subpopulations present, the structure of each state can be determined at near-atomic resolution. What we demonstrate here with GDH is that by employing three-dimensional image classification approaches, we not only can isolate distinct, coexisting conformations, but we can also localize small molecule ligands in each of these conformations. RESULTS
254 303 three-dimensional image classification approaches experimental_method Perhaps the most important contribution of these methods is the prospect that when there are discrete subpopulations present, the structure of each state can be determined at near-atomic resolution. What we demonstrate here with GDH is that by employing three-dimensional image classification approaches, we not only can isolate distinct, coexisting conformations, but we can also localize small molecule ligands in each of these conformations. RESULTS
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