Sandbox Reserved 1061: Difference between revisions
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Many thioredoxin-like proteins have a similar active site region, which includes the <scene name='69/694228/Nrdh_structure/4'>thioredoxin fold</scene>, a large turn in the protein structure right before the disulfide bond. The residues directly following the fold, <scene name='69/694228/Nrdh_structure/5'>CVQC</scene>, are the most highly conserved of all areas of the protein across multiple species. | Many thioredoxin-like proteins have a similar active site region, which includes the <scene name='69/694228/Nrdh_structure/4'>thioredoxin fold</scene>, a large turn in the protein structure right before the disulfide bond. The residues directly following the fold, <scene name='69/694228/Nrdh_structure/5'>CVQC</scene>, are the most highly conserved of all areas of the protein across multiple species. | ||
[[Image:Weblogocvqc.png|thumb|center|upright=2.5|Weblogo diagram showing highly conserved CVQC region of NrdH.]] | [[Image:Weblogocvqc.png|thumb|center|upright=2.5|Weblogo diagram showing highly conserved CVQC region of NrdH in five separate protein structures from ''Nocardiaseriolae'', ''E. coli'', ''Cornebacterium Ammoniagenes'', and ''Mycobacterium Tuberculosis''.]] | ||
==== Variable Conformations ==== | ==== Variable Conformations ==== | ||
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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, engaging a 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, engaging a 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" /> | ||
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. [[Image:Hydrophobic region pic.png|thumb| Hydrophobic region WSGFRP on the surface of MtNrdH (red) bound to ligand (green).]]<ref>DOI 10.1002/ijch.201300024</ref> <ref>PMID:21638687</ref> For this reason, it has been hypothesized that this sequence plays a role in the binding of thioredoxin reductase. <ref name="Swastik" />[[Image:Wsgfrpweblogo.png|thumb|center|upright=2.5|Weblogo diagram showing highly conserved WSGFRP region of NrdH.]] | 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. [[Image:Hydrophobic region pic.png|thumb| Hydrophobic region WSGFRP on the surface of MtNrdH (red) bound to ligand (green).]]<ref>DOI 10.1002/ijch.201300024</ref> <ref>PMID:21638687</ref> For this reason, it has been hypothesized that this sequence plays a role in the binding of thioredoxin reductase. <ref name="Swastik" />[[Image:Wsgfrpweblogo.png|thumb|center|upright=2.5|Weblogo diagram showing highly conserved WSGFRP region of NrdH in five separate protein structures from ''Nocardiaseriolae'', ''E. coli'', ''Cornebacterium Ammoniagenes'', and ''Mycobacterium Tuberculosis''.]] | ||
Arg-68 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_1/3'>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_2/2'>second conformation</scene> | Arg-68 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_1/3'>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_2/2'>second conformation</scene> | ||
