文献_Substrate Recognition Sites in Cytochrome P450 Family 2.pdfVIP

THEJOURNALOF BIOLOGICALCHEMISTRY VIII.267. No. 1. Issue 01 January 5 , pp. 8.3-90,1992 ic)1992 by The American Society for Biochemistry and Molecular Biology, Inc. I’rrnted rn 1I.S.A. Substrate Recognition Sites in CytochromeP450 Family 2 (CYPB) Proteins Inferred from ComparativeAnalyses of Amino Acid and Coding Nucleotide Sequences* (Received for publication, July 23, 1991) Osamu Gotoh$ From the Department of Biochemistry, Saitama Cancer Center Research Institute, 818 Komuro, Ina-machi, Saitama362, Japan The substrate recognition regionsin cytochrome enzymes show partial overlap but distinct substrate specific- P450 family 2(CYP2) proteins were inferred by ities. Thus it is of great interest to elucidate the molecular group-to-group alignment of CYP2 sequences and mechanisms underlying the broad but specific metabolic ca- those of bacterial P450s, including Pseudomonas pu- pacities of the mammalian P450 systems consisting of rela- tidu P450 l O l A (P450,,,), whose substrate-binding tively limited numbers of catalysts. residues have been definitely identifiedby x-ray crys- A primary question is which parts of a P450 protein are tallography of a substrate-bound form (Poulos T. L., involved in recognition or binding of substrates and hence Finzel, B. C., and Howard, A. J. (1987) J.Mol. Biol. determine the substrate specificity. There have been various 195,687-700). The six putative substrate recognition