1w0g: Difference between revisions
No edit summary |
No edit summary |
||
| Line 5: | Line 5: | ||
==Overview== | ==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 . | 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== | ||
1W0G is a | 1W0G 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 HEM and MYT as [http://en.wikipedia.org/wiki/ligands ligands]. Structure known Active Site: HEM. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1W0G OCA]. | ||
==Reference== | ==Reference== | ||
| Line 31: | Line 31: | ||
[[Category: oxidoreductase]] | [[Category: oxidoreductase]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 14:47:33 2007'' | ||
Revision as of 15:42, 5 November 2007
|
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
1W0G is a Single protein structure of sequence from Homo sapiens with HEM and MYT as ligands. Structure known Active Site: HEM. 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
Page seeded by OCA on Mon Nov 5 14:47:33 2007