1og2: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:1og2.gif|left|200px]] | [[Image:1og2.gif|left|200px]] | ||
<!-- | |||
The line below this paragraph, containing "STRUCTURE_1og2", 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_1og2| PDB=1og2 | SCENE= }} | ||
}} | |||
'''STRUCTURE OF HUMAN CYTOCHROME P450 CYP2C9''' | '''STRUCTURE OF HUMAN CYTOCHROME P450 CYP2C9''' | ||
| Line 32: | Line 29: | ||
[[Category: Ward, A.]] | [[Category: Ward, A.]] | ||
[[Category: Williams, P A.]] | [[Category: Williams, P A.]] | ||
[[Category: | [[Category: Drug metabolism,electron transport,oxidoreductase,heme]] | ||
[[Category: | [[Category: Monooxygenase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 03:48:12 2008'' | |||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | |||
Revision as of 03:48, 3 May 2008
STRUCTURE OF HUMAN CYTOCHROME P450 CYP2C9
OverviewOverview
Cytochrome P450 proteins (CYP450s) are membrane-associated haem proteins that metabolize physiologically important compounds in many species of microorganisms, plants and animals. Mammalian CYP450s recognize and metabolize diverse xenobiotics such as drug molecules, environmental compounds and pollutants. Human CYP450 proteins CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 are the major drug-metabolizing isoforms, and contribute to the oxidative metabolism of more than 90% of the drugs in current clinical use. Polymorphic variants have also been reported for some CYP450 isoforms, which has implications for the efficacy of drugs in individuals, and for the co-administration of drugs. The molecular basis of drug recognition by human CYP450s, however, has remained elusive. Here we describe the crystal structure of a human CYP450, CYP2C9, both unliganded and in complex with the anti-coagulant drug warfarin. The structure defines unanticipated interactions between CYP2C9 and warfarin, and reveals a new binding pocket. The binding mode of warfarin suggests that CYP2C9 may undergo an allosteric mechanism during its function. The newly discovered binding pocket also suggests that CYP2C9 may simultaneously accommodate multiple ligands during its biological function, and provides a possible molecular basis for understanding complex drug-drug interactions.
About this StructureAbout this Structure
1OG2 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of human cytochrome P450 2C9 with bound warfarin., Williams PA, Cosme J, Ward A, Angove HC, Matak Vinkovic D, Jhoti H, Nature. 2003 Jul 24;424(6947):464-8. Epub 2003 Jul 13. PMID:12861225 Page seeded by OCA on Sat May 3 03:48:12 2008