1og2: Difference between revisions
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==Overview== | ==Overview== | ||
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, ... | 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 Structure== | ==About this Structure== | ||
1OG2 is a | 1OG2 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with HEC as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Unspecific_monooxygenase Unspecific monooxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.14.1 1.14.14.1] Structure known Active Site: HC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1OG2 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: oxidoreductase]] | [[Category: oxidoreductase]] | ||
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Revision as of 15:58, 5 November 2007
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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 with HEC as ligand. Active as Unspecific monooxygenase, with EC number 1.14.14.1 Structure known Active Site: HC1. 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
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