| Abstract: | We determined the coding nucleotide sequence of the mRNA for a 3-methylcholanthrene-inducible cytochrome P-450, P-450d, of rat liver by sequence analysis of cloned cDNAs. The predicted amino acid sequence of the cytochrome is composed of 513 amino acids, and its NH2-terminal sequence of 30 amino acids completely coincides with that reported from analysis of the purified cytochrome P-450d. The amino acid composition of the deduced sequence also agrees well with that determined from the purified protein. Computer-aided analysis was carried out to compare the complete primary structures of five species of cytochrome P-450, two molecular species of phenobarbital-inducible rat liver cytochrome P-450 (P-450b and P-450e), phenobarbital-inducible rabbit liver cytochrome P-450LM2, 3-methylcholanthrene-inducible rat liver cytochrome P-450d, and camphor-hydroxylating P-450 of Pseudomonas putida (P-450CAM). It is concluded therefrom that the time of divergence between cytochrome P-450b (P-450e) and P-450d is much earlier than that of branching between phenobarbital-inducible cytochromes P-450 of rat and rabbit. One highly conserved cysteine-containing region that is close to the COOH terminus is found in all of these cytochrome P-450 sequences, indicating that the heme-binding site is the cysteine residue in this region. |
