1w0f
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Cytochromes P450 (P450s) metabolize a wide range of endogenous compounds | + | 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 Structure== | ==About this Structure== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Angove, H | + | [[Category: Angove, H C.]] |
[[Category: Cosme, J.]] | [[Category: Cosme, J.]] | ||
| - | [[Category: Day, P | + | [[Category: Day, P J.]] |
[[Category: Jhoti, H.]] | [[Category: Jhoti, H.]] | ||
| - | [[Category: Tickle, I | + | [[Category: Tickle, I J.]] |
| - | [[Category: Vinkovic, D | + | [[Category: Vinkovic, D M.]] |
[[Category: Vonrhein, C.]] | [[Category: Vonrhein, C.]] | ||
[[Category: Ward, A.]] | [[Category: Ward, A.]] | ||
| - | [[Category: Williams, P | + | [[Category: Williams, P A.]] |
[[Category: HEM]] | [[Category: HEM]] | ||
[[Category: STR]] | [[Category: STR]] | ||
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[[Category: oxidoreductase]] | [[Category: oxidoreductase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:39:14 2008'' |
Revision as of 13:39, 21 February 2008
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CRYSTAL STRUCTURE OF HUMAN CYTOCHROME P450 3A4
Overview
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 Structure
1W0F is a Single protein structure of sequence from Homo sapiens with and as ligands. Known structural/functional Site: . Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Feb 21 15:39:14 2008
