Recent progress in studies of the drug-metabolizing enzyme cytochrome P-450
Sogawa, K.
Gan to Kagaku Ryoho. Cancer and ChemoTherapy 13(8): 2487-2494
1986
ISSN/ISBN: 0385-0684 PMID: 3527069 Document Number: 271066
More than a dozen nearly full-length cDNA clones for cytochromes P-450 were isolated from various sources. From their nucleotide sequences, the primary structures of the corresponding proteins were deduced. All the P-450s determined showed statistically significant sequence homology among them. On the basis of this homology, the molecular evolution of the P-450 super gene family was discussed, and the functional domains of the proteins including the heme-binding site were estimated. Chromosomal DNAs for methylcholanthrene- and phenobarbital-inducible P-450s, the two inducible forms of P-450 which diverged approximately 400 million years ago, were cloned, and their gene structures were analyzed. It was interesting that all the exon-intron boundaries between the two subgene families were found not to be conserved. The mechanism of inductive expression of the methylcholanthrene-inducible P-450 c that catalyzes detrimental reactions of chemical carcinogens and mutagens such as benzopyrene were investigated by the method of DNA transfection. Several cis-acting DNA elements responsible for the regulation were located in the 5' flanking region of the P-450 c gene.