1w0f: Difference between revisions
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Revision as of 20:39, 12 November 2007
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CRYSTAL STRUCTURE OF HUMAN CYTOCHROME P450 3A4
OverviewOverview
Cytochromes P450 (P450s) metabolize a wide range of endogenous compounds, and xenobiotics, such as pollutants, environmental compounds, and drug, molecules. The microsomal, membrane-associated, P450 isoforms CYP3A4, CYP2D6, CYP2C9, CYP2C19, CYP2E1, and CYP1A2 are responsible for the, oxidative metabolism of more than 90% of marketed drugs. Cytochrome P450, 3A4 (CYP3A4) metabolizes more drug molecules than all other isoforms, combined. Here we report three crystal structures of CYP3A4: unliganded, bound to the inhibitor metyrapone, and bound to the substrate, progesterone. The structures revealed a surprisingly small active site, with little conformational change associated with the binding of either, compound. An unexpected peripheral binding site is identified, located, above a phenylalanine cluster, which may be involved in the initial, recognition of substrates or allosteric effectors.
About this StructureAbout this Structure
1W0F is a Single protein structure of sequence from Homo sapiens with HEM and STR as ligands. Structure known Active Site: AC1. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structures of human cytochrome P450 3A4 bound to metyrapone and progesterone., Williams PA, Cosme J, Vinkovic DM, Ward A, Angove HC, Day PJ, Vonrhein C, Tickle IJ, Jhoti H, Science. 2004 Jul 30;305(5684):683-6. Epub 2004 Jul 15. PMID:15256616
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