1r9o

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spinqualitylabelsall models PDB ID 1r9o Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image
, resolution 2.0Å
Ligands:	, and
Gene:	CYP2C9 (Homo sapiens)
Activity:	Unspecific monooxygenase, with EC number 1.14.14.1
Coordinates:	save as pdb, mmCIF, xml

Crystal Structure of P4502C9 with Flurbiprofen bound

Overview

The structure of human P450 2C9 complexed with flurbiprofen was determined to 2.0 A by x-ray crystallography. In contrast to other structurally characterized P450 2C enzymes, 2C5, 2C8, and a 2C9 chimera, the native catalytic domain of P450 2C9 differs significantly in the conformation of the helix F to helix G region and exhibits an extra turn at the N terminus of helix A. In addition, a distinct conformation of the helix B to helix C region allows Arg-108 to hydrogen bond with Asp-293 and Asn-289 on helix I and to interact directly with the carboxylate of flurbiprofen. These interactions position the substrate for regioselective oxidation in a relatively large active site cavity and are likely to account for the high catalytic efficiency exhibited by P450 2C9 for the regioselective oxidation of several anionic non-steroidal anti-inflammatory drugs. The structure provides a basis for interpretation of a number of observations regarding the substrate selectivity of P450 2C9 and the observed effects of mutations on catalysis.

About this Structure

1R9O is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

The structure of human cytochrome P450 2C9 complexed with flurbiprofen at 2.0-A resolution., Wester MR, Yano JK, Schoch GA, Yang C, Griffin KJ, Stout CD, Johnson EF, J Biol Chem. 2004 Aug 20;279(34):35630-7. Epub 2004 Jun 4. PMID:15181000

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