Sandbox Reserved 1061: Difference between revisions
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Many theirodoxin-like proteins have a similar active site region, denoted as the theirodoxin fold, which occurs directly before the disulfide bond. The residues in this region, denoted by letters CVQC, are the most highly conserved of all areas of the protein across multiple species. Exactly how this structure relates to function is somewhat debated. A Threonine-7 reside directly across the theirodoxin fold from the disulphide 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/8'>"A" Conformation</scene>, the alcohol of the threonine side chain points towards the disulfide bond, engaging an ionic interaction between the two that prevents the Therodoxin Reductase from binding. Alternatively, in the <scene name='69/694228/Nrdh_ligand_binding_site/12'>"B" Conformation</scene>, the alcohol points in the opposite direction, allowing sufficient space for the ligand to bind and reduction to occur.<ref>Swastik, Phulera and Mande, Shekhar C. (2013) The Crystal Structure of Mycobacterium tuberculosis NrdH at 0.87Å Suggests a Possible Mode of Its Activity. Biochemistry 52, 4056-4065.</ref> | Many theirodoxin-like proteins have a similar active site region, denoted as the theirodoxin fold, which occurs directly before the disulfide bond. The residues in this region, denoted by letters CVQC, are the most highly conserved of all areas of the protein across multiple species. Exactly how this structure relates to function is somewhat debated. A Threonine-7 reside directly across the theirodoxin fold from the disulphide 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/8'>"A" Conformation</scene>, the alcohol of the threonine side chain points towards the disulfide bond, engaging an ionic interaction between the two that prevents the Therodoxin Reductase from binding. Alternatively, in the <scene name='69/694228/Nrdh_ligand_binding_site/12'>"B" Conformation</scene>, the alcohol points in the opposite direction, allowing sufficient space for the ligand to bind and reduction to occur.<ref>Swastik, Phulera and Mande, Shekhar C. (2013) The Crystal Structure of Mycobacterium tuberculosis NrdH at 0.87Å Suggests a Possible Mode of Its Activity. Biochemistry 52, 4056-4065.</ref> | ||
The active site of the protein is stabilized through a network | The active site of the protein is stabilized through a <scene name='69/696879/Water_coordination/1'>hydrogen bond network</scene> involving the two highly conserved residues, CVQC and [http://www.proteopedia.org/wiki/index.php/Image:Weblogowsgfrp.png WSGFRP]. The crystal structure shows that interactions with one water molecule is necessary for the proper coordination between the conserved motifs to occur. These hydrogen bonds orient the important residues in the most optimal position to promote oxidation and reduction.<ref>Swastik, Phulera and Mande, Shekhar C. (2013) The Crystal Structure of Mycobacterium tuberculosis NrdH at 0.87Å Suggests a Possible Mode of Its Activity. Biochemistry 52, 4056-4065.</ref> | ||
[[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.]] | ||
