Sandbox Reserved 761: Difference between revisions
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[[Image:GDH1.jpg|frame|left|Figure 1. Each domain is colored differently - Glu-BD, NAD(P)-BD, antenna, the pivot helix. The allosteric regulators are shown as sphere models. This particular structure of GLUD1 is a combination of two X-ray structures - one with a bound GTP (1HWZ) and the second one with a bound ADP (1NQT). Although not real, this structure shows the relative position of the allosteric effectors when bound to GLUD1. NADPH and Glu are shown as well.]] | [[Image:GDH1.jpg|frame|left|Figure 1. Each domain is colored differently - Glu-BD, NAD(P)-BD, antenna, the pivot helix. The allosteric regulators are shown as sphere models. This particular structure of GLUD1 is a combination of two X-ray structures - one with a bound GTP (1HWZ) and the second one with a bound ADP (1NQT). Although not real, this structure shows the relative position of the allosteric effectors when bound to GLUD1. NADPH and Glu are shown as well.]] | ||
[[Image:closed.jpg|frame|right|Figure 2. When GDH is bound to Glutamate (blue) it's cleft is closed. ]] | |||
The NAD+ binding domains are located on top of the glutamate binding domain. These NAD+ binding domains rotate down upon the substrate and coenzyme to initiate catalysis. The NAD+ binding domain contains a forty eight-residue “antenna” that extends from the top of the NAD+ binding domain. This antenna undergoes conformational changes as the cleft of the active site opens and closes (2). Both of the domains are positioned differently in GDH. <scene name='56/564037/Open_cleft/1'>When GDH is not bound by glutamate its cleft is open</scene>, however, when GDH is bound by 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. | The NAD+ binding domains are located on top of the glutamate binding domain. These NAD+ binding domains rotate down upon the substrate and coenzyme to initiate catalysis. The NAD+ binding domain contains a forty eight-residue “antenna” that extends from the top of the NAD+ binding domain. This antenna undergoes conformational changes as the cleft of the active site opens and closes (2). Both of the domains are positioned differently in GDH. <scene name='56/564037/Open_cleft/1'>When GDH is not bound by glutamate its cleft is open</scene>, however, when GDH is bound by 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. | ||
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. 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.[1] | 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. 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.[1] | ||
