A full-length cDNA clone (1,894 homology, and nucleotides 1068 to 1260, 69Z homology, with portions of rat P-450b exons 2 and 7, respectively. P3-450 shows 62% homology in the socalled "highly conserved region" of 39 nucleotides in the rat P-450b and P-450e and the mouse P-450b. These results indicate that P3-450, P-450b and P-450e arose from a common ancestral gene. Cysteinyl peptide-coding regions were examined: P3-450 nucleotides 1405 to 1464 exhibit 61% homology, and nucleotides 502 to 552 exhibit 37% homology, when compared with their corresponding regions in the rat P-450b gene. These data support the likelihood that cysteine 456 is the thiolate ligand to the heme iron in the P3-450 enzyme active-site.
INTRODUCTIONA large portion of drug-metabolizing enzyme activity arises from the membrane-bound multicomponent cytochrome P-450 system (1, 2). Endogenous substrates of P-450 include steroids, fatty acids, biogenic amines, prostaglandins and leukotrienes. Foreign substrates include almost all drugs, chemical carcinogens, and other environmental pollutants numbering in the tens of thousands; hence, the recommended nomenclature for P-450-mediated catalytic activity is "multisubstrate monooxygenase" (3).