Structures of cysteine-containing peptides in isosafrole-inducible rat hepatic microsomal cytochrome P-450d: sequence homology with 3-methylcholanthrene-induced cytochrome P-450c.
Six cysteine-containing tryptic peptides were isolated from rat liver cytochrome P-450d, the major isosafrole-induced isozyme, by reversed-phase high performance liquid chromatography. The six peptides contained a total of seven cysteine residues. Five of the peptides have significant sequence homology (20/22, 10/16, 8/13, 13/18, and 5/9 identical residues) to cysteine-containing peptides in cytochrome P-450c, the major isozyme induced by 3-methylcholanthrene. One of the peptides (partial sequence, Cys-Ile-Gly-Glu-Ile-Pro-Ala-Lys-Trp-Glu-Val-Phe-Leu-) can be included in the highly conserved COOH-terminal domain found in all cytochromes P-450 that have been sequenced. Although this domain has been postulated as the heme-binding domain by some investigators, it is not homologous to the heme-binding region in cytochrome P-450cam. A second peptide (partial sequence, Asp-Pro-Thr-Ser-Val-Ser-Ser-Cys-Tyr-Leu-Glu-Glu-His-Val-Ser-Lys) is, however, a possible candidate for the heme attachment site to cysteine because of its weak homology to the heme-binding site in cytochrome P-450cam. These results indicate that either the location of the heme-binding site is different in various forms of cytochromes P-450 or the amino acid sequence surrounding the heme-binding cysteine is not highly conserved among these proteins.
D000595:Amino Acid Sequence; D000818:Animals; D003545:Cysteine / Q000032:analysis; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis* / Q000096:biosynthesis; D004149:Dioxoles / Q000494:pharmacology*; D004790:Enzyme Induction; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology*; D008862:Microsomes, Liver / Q000201:enzymology*; D010105:Oxygenases / Q000378:metabolism; D010446:Peptide Fragments / Q000032:analysis; D051381:Rats; D012451:Safrole / Q000494:pharmacology*; D014357:Trypsin / Q000378:metabolism
D004149:Dioxoles; D010446:Peptide Fragments; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; D014357:Trypsin; D003545:Cysteine; D012451:Safrole; C015959:isosafrole