CYP2C9 catalytic domain showing positions of *2 and *3 polymorphisms

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Publication Type Multimedia
School or College College of Pharmacy
Department Pharmacology & Toxicology
Creator Blumenthal, Donald K.
Title CYP2C9 catalytic domain showing positions of *2 and *3 polymorphisms
Date 2006-08-30
Description X-ray crystal structure of human CYP2C9 (PDB id=1R9O (http://www.rcsb.org/pdb/cgi/explore.cgi?pdbId=1R9O)) showing the positions of the amino acids altered by the CYP2C9*2 (Arg144Cys) and CYP2C9*3 (Ile359Leu) polymorphisms relative to the six substrate recognition sites (SRSs). The Arg144 and Ile359 sidechains are shown as space-filling spheres colored according to element type (C=white, N=blue, O=red). The heme group is also colored according to element (Fe=orange). The key sidechains in each of the six SRSs are colored according to SRS: SRS1 (red; Val113, Phe114); SRS2 (orange; Ile205, Leu208); SRS3 (yellow; Val237, Met240); SRS4 (green; Gly296, Ala297); SRS5 (blue; Leu366); SRS6 (magenta; Phe 476). The CYP2C9*2 (Arg144Cys) allele is thought to give rise to a form of CYP2C9 with reduced affinity for its cofactor, P450 reductase. The P450 activity of the enzyme resulting from the CYP2C9*3 (Ile359Leu) allele has a lower Vmax and lower substrate Km than wild type CYP2C9, presumably due to indirect conformational effects of the sidechain substitution on the enzyme active site. Figure and animation were created using PyMol.
Publisher The McGraw-Hill Companies http://www.accessmedicine.com/resourceToc.aspx?resourceID=28

PyMol file (952 KB): http://ir.utah.edu/blumenthal/PyMol/CYP2C9_1R9O_Aug3.pse

Download PyMol software to view this file. Available for free educational use:
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Quicktime Movie--Medium Resolution (4 MB): http://ir.utah.edu/blumenthal/structure/warfarin/CYP2C9_medres.mov

Quicktime Movie--Low Resolution (1 MB): http://ir.utah.edu/blumenthal/structure/warfarin/CYP2C9_small_medres.mov
Subject Warfarin; CYP2C9*2; CYP2C9*3; P450
Bibliographic Citation Rettie, Alan E.; Rieder, Mark J. Hot Topic: Warfarin Pharmacogenomics. Goodman & Gilman's The Pharmacological Basis of Therapeutics, (11th Ed). Laurence L. Brunton (ed). Retrieved September 11, 2006 from http://www.accessmedicine.com/updatesContent.aspx?aid=1000935
Rights Management Copyright ©2006 The McGraw-Hill Companies. All rights reserved.
Format Medium image/jpeg (visual file)
Identifier Ir-main,375
ARK ark:/87278/s61g14z7
Setname ir_uspace
Date Created 2012-07-31
Date Modified 2012-07-31
ID 707889
Reference URL https://collections.lib.utah.edu/ark:/87278/s61g14z7
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