This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
1r9o
From Proteopedia
| Line 1: | Line 1: | ||
[[Image:1r9o.gif|left|200px]] | [[Image:1r9o.gif|left|200px]] | ||
| - | + | <!-- | |
| - | + | The line below this paragraph, containing "STRUCTURE_1r9o", creates the "Structure Box" on the page. | |
| - | + | You may change the PDB parameter (which sets the PDB file loaded into the applet) | |
| - | + | or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |
| - | + | or leave the SCENE parameter empty for the default display. | |
| - | + | --> | |
| - | + | {{STRUCTURE_1r9o| PDB=1r9o | SCENE= }} | |
| - | + | ||
| - | + | ||
| - | }} | + | |
'''Crystal Structure of P4502C9 with Flurbiprofen bound''' | '''Crystal Structure of P4502C9 with Flurbiprofen bound''' | ||
| Line 32: | Line 29: | ||
[[Category: Wester, M R.]] | [[Category: Wester, M R.]] | ||
[[Category: Yano, J K.]] | [[Category: Yano, J K.]] | ||
| - | [[Category: | + | [[Category: Drug metabolizing enzyme]] |
| - | [[Category: | + | [[Category: Heme]] |
| - | [[Category: | + | [[Category: Monooxygenase]] |
| - | [[Category: | + | [[Category: Oxidoreductase]] |
| - | [[Category: | + | [[Category: P450]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 07:14:45 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 04:14, 3 May 2008
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 Page seeded by OCA on Sat May 3 07:14:45 2008
