Complete amino acid sequence and predicted membrane topology of phenobarbital-induced cytochrome P-450 (isozyme 2) from rabbit liver microsomes.

Abstract

The complete amino acid sequence of phenobarbital-induced isozyme 2 of rabbit liver microsomal cytochrome P-450 (P-450LM2) is presented. The polypeptide consists of 491 residues with a calculated MW of 55, 755. The rabbit isozyme is 77% identical to the corresponding rat cytochrome, P-450b, as deduced from cDNA, with 96% of the hydrophobic, 88% of the anionic, and 83% of the cationic positions conserved. The secondary structure of isozyme 2 was predicted and a model was developed for the membrane topology of this cytochrome. Of the 2 highly conserved cysteinyl peptides in P-450LM2, P-450b and bacterial [Pseudomonas putida] P-450cam, on the basis of the model, the one nearer the NH2 terminus (Cys-152 in P-450LM2) is favored as the source of the thiolate ligand to the heme Fe atom. The recently reported sequence of the apparently identical protein has 2 fewer residues and differs in 14 other amino acid assignments.