{PDOC00081} {PS00086; CYTOCHROME_P450} {BEGIN} ******************************************************* * Cytochrome P450 cysteine heme-iron ligand signature * ******************************************************* Cytochrome P450's [1,2,3] are a group of enzymes involved in the oxidative metabolism of a high number of natural compounds (such as steroids, fatty acids, prostaglandins, leukotrienes, etc) as well as drugs, carcinogens and mutagens. Based on sequence similarities, P450's have been classified into about forty different families [4,5]. P450's are proteins of 400 to 530 amino acids; the only exception is Bacillus BM-3 (CYP102) which is a protein of 1048 residues that contains a N-terminal P450 domain followed by a reductase domain. P450's are heme proteins. A conserved cysteine residue in the C- terminal part of P450's is involved in binding the heme iron in the fifth coordination site. From a region around this residue, we developed a ten residue signature specific to P450's. -Consensus pattern: [FW]-[SGNH]-x-[GD]-{F}-[RKHPT]-{P}-C-[LIVMFAP]-[GAD] [C is the heme iron ligand] -Sequences known to belong to this class detected by the pattern: ALL, except for P450 IIB10 from mouse, which has Lys in the first position of the pattern. -Other sequence(s) detected in Swiss-Prot: 9. -Note: The term 'cytochrome' P450, while commonly used, is incorrect as P450 are not electron-transfer proteins; the appropriate name is P450 'heme- thiolate proteins'. -Expert(s) to contact by email: Degtyarenko K.N.; kirill@ebi.ac.uk -Last update: December 2004 / Pattern and text revised. [ 1] Nebert D.W., Gonzalez F.J. "P450 genes: structure, evolution, and regulation." Annu. Rev. Biochem. 56:945-993(1987). PubMed=3304150; DOI=10.1146/annurev.bi.56.070187.004501 [ 2] Coon M.J., Ding X.X., Pernecky S.J., Vaz A.D. "Cytochrome P450: progress and predictions." FASEB J. 6:669-673(1992). PubMed=1537454 [ 3] Guengerich F.P. "Reactions and significance of cytochrome P-450 enzymes." J. Biol. Chem. 266:10019-10022(1991). PubMed=2037557 [ 4] Nelson D.R., Kamataki T., Waxman D.J., Guengerich F.P., Estabrook R.W., Feyereisen R., Gonzalez F.J., Coon M.J., Gunsalus I.C., Gotoh O. "The P450 superfamily: update on new sequences, gene mapping, accession numbers, early trivial names of enzymes, and nomenclature." DNA Cell Biol. 12:1-51(1993). PubMed=7678494 [ 5] Degtyarenko K.N., Archakov A.I. "Molecular evolution of P450 superfamily and P450-containing monooxygenase systems." FEBS Lett. 332:1-8(1993). PubMed=8405421 -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}