| anno_start anno_end anno_text entity_type sentence section | |
| 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 | |