1W0G
Crystal structure of human cytochrome P450 3A4
Summary for 1W0G
| Entry DOI | 10.2210/pdb1w0g/pdb |
| Related | 1W0E 1W0F |
| Descriptor | CYTOCHROME P450 3A4, METYRAPONE, PROTOPORPHYRIN IX CONTAINING FE, ... (4 entities in total) |
| Functional Keywords | oxidoreductase, nifedipine oxidase, cytochrome p450, electron transport, monooxygenase |
| Biological source | HOMO SAPIENS (HUMAN) |
| Total number of polymer chains | 1 |
| Total formula weight | 56324.24 |
| Authors | Williams, P.A.,Cosme, J.,Vinkovic, D.M.,Ward, A.,Angove, H.C.,Day, P.J.,Vonrhein, C.,Tickle, I.J.,Jhoti, H. (deposition date: 2004-06-03, release date: 2004-07-22, Last modification date: 2023-12-13) |
| Primary citation | Williams, P.A.,Cosme, J.,Vinkovic, D.M.,Ward, A.,Angove, H.C.,Day, P.J.,Vonrhein, C.,Tickle, I.J.,Jhoti, H. Crystal Structures of Human Cytochrome P450 3A4 Bound to Metyrapone and Progesterone Science, 305:683-, 2004 Cited by PubMed Abstract: 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. PubMed: 15256616DOI: 10.1126/SCIENCE.1099736 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.73 Å) |
Structure validation
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