Sandbox Reserved 1061: Difference between revisions
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Exactly how this structure relates to function is somewhat debated, but it is hypothesized that the fold allows residues preceding the turn to interact with the CVQC motif after the turn. A threonine-7 reside directly across the thioredoxin fold from the disulfide bond has been suggested to adopt two different conformations which differentially affect the redox abilities of the protein. In the <scene name='69/694228/Nrdh_ligand_binding_site/17'>"A" conformation</scene>, the alcohol oxygen of the threonine side chain (seen as a red ball) points towards the disulfide bond, forming an electrostatic interaction (represented by a short dashed line) between the two that prevents thioredoxin reductase from binding. Alternatively, in the <scene name='69/694228/Nrdh_ligand_binding_site/16'>"B" Conformation</scene>, the alcohol points in the opposite direction, allowing sufficient space and enough electrostatic freedom for the ligand to bind and reduction to occur.<ref name="Swastik" /> | Exactly how this structure relates to function is somewhat debated, but it is hypothesized that the fold allows residues preceding the turn to interact with the CVQC motif after the turn. A threonine-7 reside directly across the thioredoxin fold from the disulfide bond has been suggested to adopt two different conformations which differentially affect the redox abilities of the protein. In the <scene name='69/694228/Nrdh_ligand_binding_site/17'>"A" conformation</scene>, the alcohol oxygen of the threonine side chain (seen as a red ball) points towards the disulfide bond, forming an electrostatic interaction (represented by a short dashed line) between the two that prevents thioredoxin reductase from binding. Alternatively, in the <scene name='69/694228/Nrdh_ligand_binding_site/16'>"B" Conformation</scene>, the alcohol points in the opposite direction, allowing sufficient space and enough electrostatic freedom for the ligand to bind and reduction to occur.<ref name="Swastik" /> | ||
[[Image:Hydrophobic region pic.png|thumb|right| Hydrophobic region WSGFRP on the surface of MtNrdH (red) bound to ligand (green).<ref name="PyMol">The PyMOL Molecular Graphics System, Version 1.7.4 Schrödinger, LLC.</ref>]] | |||
Another highly conserved series of residues is the WSGFRP sequence. This nonpolar sequence is found on the surface of the molecule and is exposed to solvent. For this reason, it has been hypothesized that this sequence plays a role in the binding of thioredoxin reductase. <ref name="Swastik" /> | |||
<scene name='69/694227/Arg_68/4'>Arg-68</scene> is responsible for the stabilization of the hydrophobic region of NrdH. Arg-68 has two distinct conformations. In the <scene name='69/694227/Arg_68_conformation_1/4'>first conformation</scene>, Arg-68 is hydrogen bonded to His- 60 and Asp-59. When Arg-68 shifts to its <scene name='69/694227/Arg_68_conformation_2/5'>second conformation</scene>, it breaks its hydrogen bond with Asp-59. <ref name="Swastik" /> This reduction in hydrogen bonding gives the hydrophobic region more flexibility and is thought to occur when NrdH is in its inactive state. | <scene name='69/694227/Arg_68/4'>Arg-68</scene> is responsible for the stabilization of the hydrophobic region of NrdH. Arg-68 has two distinct conformations. In the <scene name='69/694227/Arg_68_conformation_1/4'>first conformation</scene>, Arg-68 is hydrogen bonded to His- 60 and Asp-59. When Arg-68 shifts to its <scene name='69/694227/Arg_68_conformation_2/5'>second conformation</scene>, it breaks its hydrogen bond with Asp-59. <ref name="Swastik" /> This reduction in hydrogen bonding gives the hydrophobic region more flexibility and is thought to occur when NrdH is in its inactive state. | ||
[[Image:Wsgfrpweblogo.png|thumb|center|upright=2.5|Weblogo diagram showing highly conserved WSGFRP region of NrdH in four separate protein structures from ''Nocardia seriolae'', ''E. coli'', ''Cornebacterium Ammoniagenes'', and ''Mycobacterium Tuberculosis''.<ref name="weblogo" />]] | |||
==== Stabilization ==== | ==== Stabilization ==== | ||
