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3t3r

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Human Cytochrome P450 2A6 in complex with Pilocarpine

Structural highlights

3t3r is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.4Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CP2A6_HUMAN Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Constitutes the major nicotine C-oxidase. Acts as a 1,4-cineole 2-exo-monooxygenase. Possesses low phenacetin O-deethylation activity.^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

References

↑ Maurice M, Emiliani S, Dalet-Beluche I, Derancourt J, Lange R. Isolation and characterization of a cytochrome P450 of the IIA subfamily from human liver microsomes. Eur J Biochem. 1991 Sep 1;200(2):511-7. PMID:1889415
↑ Yun CH, Shimada T, Guengerich FP. Purification and characterization of human liver microsomal cytochrome P-450 2A6. Mol Pharmacol. 1991 Nov;40(5):679-85. PMID:1944238
↑ Miyazawa M, Shindo M, Shimada T. Roles of cytochrome P450 3A enzymes in the 2-hydroxylation of 1,4-cineole, a monoterpene cyclic ether, by rat and human liver microsomes. Xenobiotica. 2001 Oct;31(10):713-23. PMID:11695850 doi:10.1080/00498250110065595
↑ Yano JK, Hsu MH, Griffin KJ, Stout CD, Johnson EF. Structures of human microsomal cytochrome P450 2A6 complexed with coumarin and methoxsalen. Nat Struct Mol Biol. 2005 Sep;12(9):822-3. Epub 2005 Aug 7. PMID:16086027 doi:http://dx.doi.org/10.1038/nsmb971
↑ Yano JK, Denton TT, Cerny MA, Zhang X, Johnson EF, Cashman JR. Synthetic inhibitors of cytochrome P-450 2A6: inhibitory activity, difference spectra, mechanism of inhibition, and protein cocrystallization. J Med Chem. 2006 Nov 30;49(24):6987-7001. PMID:17125252 doi:http://dx.doi.org/10.1021/jm060519r
↑ DeVore NM, Smith BD, Urban MJ, Scott EE. Key residues controlling phenacetin metabolism by human cytochrome P450 2A enzymes. Drug Metab Dispos. 2008 Dec;36(12):2582-90. Epub 2008 Sep 8. PMID:18779312 doi:10.1124/dmd.108.023770