Sandbox Reserved 761: Difference between revisions

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[[Image:closed.jpg|frame|right|Figure 3. When GDH is bound to Glutamate (blue) it's cleft is closed. ]]

Located on top of the glutamate binding domain, these NAD+ binding domains rotate down upon the substrate and coenzyme to initiate catalysis. The 48-residue antenna that extends from the top of the NAD+ binding domain undergoes conformational changes as the cleft of the active site opens and closes <ref>PMID:12653548</ref>. When GDH is not bound by glutamate its cleft is open, however, when GDH is bound to glutamate it is closed. This position difference between the two domains allows the cleft to be closed, which brings the C4 of the nicotinamide ring and the alpha carbon of the glutamate substrate into the appropriate orientation for a hydride transfer to occur. Residues 200-206, 375-379, and 421-423 are critical for the control of the hinges that open or close the cleft between the two domains <ref>PMID:9405044</ref>. ~~These residues are colored <scene name='56/564037/Open_cleft2/1'>green.</scene>~~ The residues that form this hinge, which allow the cleft to open or close are both near and far from the active site. The <scene name='56/564037/Active_site_final/1'>active site</scene> of GDH is composed of residues: 209-210, 213, 217, 261, 265, 289, 292, 450.

Located on top of the glutamate binding domain, these NAD+ binding domains rotate down upon the substrate and coenzyme to initiate catalysis. The 48-residue antenna that extends from the top of the NAD+ binding domain undergoes conformational changes as the cleft of the active site opens and closes <ref>PMID:12653548</ref>. When GDH is not bound by glutamate its cleft is open, however, when GDH is bound to glutamate it is closed. This position difference between the two domains allows the cleft to be closed, which brings the C4 of the nicotinamide ring and the alpha carbon of the glutamate substrate into the appropriate orientation for a hydride transfer to occur. Residues 200-206, 375-379, and 421-423 are critical for the control of the hinges that open or close the cleft between the two domains <ref>PMID:9405044</ref>. The residues that form this hinge, which allow the cleft to open or close are both near and far from the active site. The <scene name='56/564037/Active_site_final/1'>active site</scene> of GDH is composed of residues: 209-210, 213, 217, 261, 265, 289, 292, 450.

The N-terminal glutamate (Glu) binding domains, composed of mainly beta sheets, are mainly responsible in the build up of the core structure of the hexamer, a stacked dimer of trimers. The NAD+ binding domain and Glu binding domain form the catalytic cleft. During substrate binding, the NAD+ binding domain moves significantly. NAD+ cofactor binds at the C-terminal end of the parallel beta strands in the N-domain, lying in the cleft between the N and C-domains. The glutamate substrate binds deep in this cleft, with the side chain of the glutamate lying in a pocket on the enzyme surface. Residues 193-204, and 383-393 are essential for the glutamate to bind in the cleft <ref>PMID:9405044</ref>. These residues are colored <scene name='56/564037/Domains1/1'>green</scene> <ref>PMID:9405044</ref>. This movement has two components, rotating along the long axis of a helix at the back of the NAD+ binding domain, called "the pivot helix", and twisting about the antenna in a clockwise fashion. A comparison of the open and closed conformations of GDH reveals changes in the small helix of the descending strand of the antenna, which seems to recoil as the catalytic cleft opens <ref>PMID:12054821</ref>.

The N-terminal glutamate (Glu) binding domains, composed of mainly beta sheets, are mainly responsible in the build up of the core structure of the hexamer, a stacked dimer of trimers. The NAD+ binding domain and Glu binding domain form the catalytic cleft. During substrate binding, the NAD+ binding domain moves significantly. NAD+ cofactor binds at the C-terminal end of the parallel beta strands in the N-domain, lying in the cleft between the N and C-domains. The glutamate substrate binds deep in this cleft, with the side chain of the glutamate lying in a pocket on the enzyme surface. Residues 193-204, and 383-393 are essential for the glutamate to bind in the cleft <ref>PMID:9405044</ref>. These residues are colored <scene name='56/564037/Domains1/1'>green</scene> <ref>PMID:9405044</ref>. This movement has two components, rotating along the long axis of a helix at the back of the NAD+ binding domain, called "the pivot helix", and twisting about the antenna in a clockwise fashion. A comparison of the open and closed conformations of GDH reveals changes in the small helix of the descending strand of the antenna, which seems to recoil as the catalytic cleft opens <ref>PMID:12054821</ref>. The Glu binding domains of the monomers are position as such that the rotation about the pivot helix in each monomer is not restricted. The antennae from three subunits within the trimers wrap around each other and undergo conformational changes as the catalytic cleft opens and closes. The antenna serves as an intersubunit communication conduit during negative cooperativity and allosteric regulation.

The Glu binding domains of the monomers are position as such that the rotation about the pivot helix in each monomer is not restricted. The antennae from three subunits within the trimers wrap around each other and undergo conformational changes as the catalytic cleft opens and closes. The antenna serves as an intersubunit communication conduit during negative cooperativity and allosteric regulation.

==Glutamate Dehydrogenase Mechanism==

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@@ Line 24: / Line 24: @@
 [[Image:closed.jpg|frame|right|Figure 3. When GDH is bound to Glutamate (blue) it's cleft is closed. ]]
-Located on top of the glutamate binding domain, these NAD+ binding domains rotate down upon the substrate and coenzyme to initiate catalysis.  The 48-residue antenna that extends from the top of the NAD+ binding domain undergoes conformational changes as the cleft of the active site opens and closes <ref>PMID:12653548</ref>. When GDH is not bound by glutamate its cleft is open, however, when GDH is bound to glutamate it is closed. This position difference between the two domains allows the cleft to be closed, which brings the C4 of the nicotinamide ring and the alpha carbon of the glutamate substrate into the appropriate orientation for a hydride transfer to occur. Residues 200-206, 375-379, and 421-423 are critical for the control of the hinges that open or close the cleft between the two domains <ref>PMID:9405044</ref>. These residues are colored <scene name='56/564037/Open_cleft2/1'>green.</scene> The residues that form this hinge, which allow the cleft to open or close are both near and far from the active site.  The <scene name='56/564037/Active_site_final/1'>active site</scene> of GDH is composed of residues: 209-210, 213, 217, 261, 265, 289, 292, 450.
+Located on top of the glutamate binding domain, these NAD+ binding domains rotate down upon the substrate and coenzyme to initiate catalysis.  The 48-residue antenna that extends from the top of the NAD+ binding domain undergoes conformational changes as the cleft of the active site opens and closes <ref>PMID:12653548</ref>. When GDH is not bound by glutamate its cleft is open, however, when GDH is bound to glutamate it is closed. This position difference between the two domains allows the cleft to be closed, which brings the C4 of the nicotinamide ring and the alpha carbon of the glutamate substrate into the appropriate orientation for a hydride transfer to occur. Residues 200-206, 375-379, and 421-423 are critical for the control of the hinges that open or close the cleft between the two domains <ref>PMID:9405044</ref>. The residues that form this hinge, which allow the cleft to open or close are both near and far from the active site.  The <scene name='56/564037/Active_site_final/1'>active site</scene> of GDH is composed of residues: 209-210, 213, 217, 261, 265, 289, 292, 450.
-The N-terminal glutamate (Glu) binding domains, composed of mainly beta sheets, are mainly responsible in the build up of the core structure of the hexamer, a stacked dimer of trimers. The NAD+ binding domain and Glu binding domain form the catalytic cleft. During substrate binding, the NAD+ binding domain moves significantly. NAD+ cofactor binds at the C-terminal end of the parallel beta strands in the N-domain, lying in the cleft between the N and C-domains. The glutamate substrate binds deep in this cleft, with the side chain of the glutamate lying in a pocket on the enzyme surface.  Residues 193-204, and 383-393 are essential for the glutamate to bind in the cleft <ref>PMID:9405044</ref>. These residues are colored <scene name='56/564037/Domains1/1'>green</scene> <ref>PMID:9405044</ref>.   This movement has two components, rotating along the long axis of a helix at the back of the NAD+ binding domain, called "the pivot helix", and twisting about the antenna in a clockwise fashion. A comparison of the open and closed conformations of GDH reveals changes in the small helix of the descending strand of the antenna, which seems to recoil as the catalytic cleft opens <ref>PMID:12054821</ref>.
+The N-terminal glutamate (Glu) binding domains, composed of mainly beta sheets, are mainly responsible in the build up of the core structure of the hexamer, a stacked dimer of trimers. The NAD+ binding domain and Glu binding domain form the catalytic cleft. During substrate binding, the NAD+ binding domain moves significantly. NAD+ cofactor binds at the C-terminal end of the parallel beta strands in the N-domain, lying in the cleft between the N and C-domains. The glutamate substrate binds deep in this cleft, with the side chain of the glutamate lying in a pocket on the enzyme surface.  Residues 193-204, and 383-393 are essential for the glutamate to bind in the cleft <ref>PMID:9405044</ref>. These residues are colored <scene name='56/564037/Domains1/1'>green</scene> <ref>PMID:9405044</ref>.   This movement has two components, rotating along the long axis of a helix at the back of the NAD+ binding domain, called "the pivot helix", and twisting about the antenna in a clockwise fashion. A comparison of the open and closed conformations of GDH reveals changes in the small helix of the descending strand of the antenna, which seems to recoil as the catalytic cleft opens <ref>PMID:12054821</ref>. The Glu binding domains of the monomers are position as such that the rotation about the pivot helix in each monomer is not restricted. The antennae from three subunits within the trimers wrap around each other and undergo conformational changes as the catalytic cleft opens and closes. The antenna serves as an intersubunit communication conduit during negative cooperativity and allosteric regulation.
-The Glu binding domains of the monomers are position as such that the rotation about the pivot helix in each monomer is not restricted. The antennae from three subunits within the trimers wrap around each other and undergo conformational changes as the catalytic cleft opens and closes. The antenna serves as an intersubunit communication conduit during negative cooperativity and allosteric regulation.
 ==Glutamate Dehydrogenase Mechanism==