User:Adam Mirando/Sandbox 1: Difference between revisions
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== Structure == | == Structure == | ||
<applet load='1FO4' size='300' frame='true' align='right' caption=' | <applet load='1FO4' size='300' frame='true' align='right' caption='Bovine Milk Xanthine Dehydrogenase' /> | ||
Bovine xanthine dehydrogenase has the overall dimensions 155 Ǻ x 90 Ǻ x 70 Ǻ in its dimeric form and 100 Ǻ x 90 Ǻ x 70 Ǻ for the individual protomers. The overall structure of the enzyme can be categorized into three key domains. The <scene name='User:Adam_Mirando/Sandbox_1/Xdh_domain/3'>N-terminal domain</scene> (green, residues 1- 165) harbors the two [http://en.wikipedia.org/wiki/Iron-sulfur_cluster Fe-S clusters] (shown in yellow). The second, <scene name='User:Adam_Mirando/Sandbox_1/Xdh_domain/3'>middle domain</scene> (blue, residues 226-531) contains the FAD domain (shown in orange) and the NAD<sup>+</sup>/O<sub>2</sub> binding site. The <scene name='User:Adam_Mirando/Sandbox_1/Xdh_domain/3'>C-terminal domain</scene> (purple, residues 590-1332) contains the [http://en.wikipedia.org/wiki/Molybdopterin molybdopterin] cofactor (shown in red) and is positioned close to the interface between the other two domains. This structure allows for interactions between co-factors of the same [http://en.wikipedia.org/wiki/Protomer protomer]. However, closest distance of co-factors between the two subunits is greater than 50 Ǻ, suggesting that the two subunits do not cross communicate <ref name="structure">PMID:11005854</ref>. | Bovine xanthine dehydrogenase has the overall dimensions 155 Ǻ x 90 Ǻ x 70 Ǻ in its dimeric form and 100 Ǻ x 90 Ǻ x 70 Ǻ for the individual protomers. The overall structure of the enzyme can be categorized into three key domains. The <scene name='User:Adam_Mirando/Sandbox_1/Xdh_domain/3'>N-terminal domain</scene> (green, residues 1- 165) harbors the two [http://en.wikipedia.org/wiki/Iron-sulfur_cluster Fe-S clusters] (shown in yellow). The second, <scene name='User:Adam_Mirando/Sandbox_1/Xdh_domain/3'>middle domain</scene> (blue, residues 226-531) contains the FAD domain (shown in orange) and the NAD<sup>+</sup>/O<sub>2</sub> binding site. The <scene name='User:Adam_Mirando/Sandbox_1/Xdh_domain/3'>C-terminal domain</scene> (purple, residues 590-1332) contains the [http://en.wikipedia.org/wiki/Molybdopterin molybdopterin] cofactor (shown in red) and is positioned close to the interface between the other two domains. This structure allows for interactions between co-factors of the same [http://en.wikipedia.org/wiki/Protomer protomer]. However, closest distance of co-factors between the two subunits is greater than 50 Ǻ, suggesting that the two subunits do not cross communicate <ref name="structure">PMID:11005854</ref>. | ||
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===Substrate Binding and Intermediate Stabilization=== | ===Substrate Binding and Intermediate Stabilization=== | ||
<applet load='3BDJ' size='300' frame='true' align='right' caption=' | <applet load='3BDJ' size='300' frame='true' align='right' caption='Bovine Milk Xanthine Dehydrogenase' /> | ||
Several active site residues have been implicated in the substrate binding and catalytic roles of xanthine oxidoreductase. The molybdenum center is accessible only through a 5 Ǻ x 3 Ǻ channel that is 5 Ǻ deep. The active site pocket itself is lined by several <scene name='User:Adam_Mirando/Sandbox_1/Active_site_residues/1'>conserved residues</scene>: Glu802, Leu873, Arg880, Phe914, Phe1009, and Glu1261 <ref name="SubOri" /><ref name="sequence">11796116</ref>. The several [http://en.wikipedia.org/wiki/Hydrophobic hydrophobic] residues, Leu873, Phe914, and Phe1009, serve to form the active site pocket<ref name="SubOri" /><ref name="sequence" />. The conserved Glu1261 <ref name="gluarg" /> is located near the molybdopterin co-factor (see “Xanthine Oxidation Mechanism” above”) and acts as a general base to extract a proton from the hydroxyl group of the molybdenum center. The complete loss of enzymatic activity following mutations of this residue confirms its important role in catalysis <ref name="hypoxanthine" />. Arg880 and Glu802 are thought to be involved in the mechanism through the formation of stabilizing interactions with the reaction intermediates <ref name="gluarg" /><ref name="SubOri" /><ref name="hypoxanthine" />. | Several active site residues have been implicated in the substrate binding and catalytic roles of xanthine oxidoreductase. The molybdenum center is accessible only through a 5 Ǻ x 3 Ǻ channel that is 5 Ǻ deep. The active site pocket itself is lined by several <scene name='User:Adam_Mirando/Sandbox_1/Active_site_residues/1'>conserved residues</scene>: Glu802, Leu873, Arg880, Phe914, Phe1009, and Glu1261 <ref name="SubOri" /><ref name="sequence">11796116</ref>. The several [http://en.wikipedia.org/wiki/Hydrophobic hydrophobic] residues, Leu873, Phe914, and Phe1009, serve to form the active site pocket<ref name="SubOri" /><ref name="sequence" />. The conserved Glu1261 <ref name="gluarg" /> is located near the molybdopterin co-factor (see “Xanthine Oxidation Mechanism” above”) and acts as a general base to extract a proton from the hydroxyl group of the molybdenum center. The complete loss of enzymatic activity following mutations of this residue confirms its important role in catalysis <ref name="hypoxanthine" />. Arg880 and Glu802 are thought to be involved in the mechanism through the formation of stabilizing interactions with the reaction intermediates <ref name="gluarg" /><ref name="SubOri" /><ref name="hypoxanthine" />. | ||