1w0e | pdb_00001w0e

Crystal structure of human cytochrome P450 3A4

spinqualitylabelsall models 1w0e, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1w0e is a 1 chain structure with sequence from Homo sapiens. The October 2006 RCSB PDB Molecule of the Month feature on Cytochrome p450 by David S. Goodsell is 10.2210/rcsb_pdb/mom_2006_10. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.8Å Ligands: HEM Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CP3A4_HUMAN Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Cytochrome P450 3D structures

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