title: Membrane topology of the mammalian P450 cytochromes.
abstract: The membrane topology of the mammalian P450 cytochromes has been studied intensively by computational approaches, proteolysis, chemical modification, genetic engineering, and immunochemistry. Initial results for the cytochromes of the endoplasmic reticulum appeared to indicate a polytopic, four to eight transmembrane anchor model with an active site buried in the membrane. However, recent findings show that the microsomal P450s are bound to the endoplasmic reticulum by only one or two transmembrane peptides located at the NH2-terminal end, and that the active site is part of a large cytoplasmic domain that may have one or two additional peripheral membrane contacts. The membrane-bound state is viewed as rather rigid, and the plane of the heme lies between perpendicular and parallel to the plane of the endoplasmic reticulum. The mitochondrial P450 cytochromes lack a hydrophobic NH2 terminus in the mature form, and thus differ from the microsomal isozymes in this significant way. However, although the exact topology of cytochrome P450 in the inner mitochondrial membrane remains to be elucidated, certain features are clearly comparable to those of microsomal P450. Therefore, the membrane topology of the P450 gene superfamily may follow a similar pattern.
authors.affiliation: Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Ohio State University, Columbus.
authors.forename: S D
authors.initials: SD
authors.lastname: Black
mesh_terms: D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000201:enzymology / Q000648:ultrastructure; D005818:Genetic Engineering; D007425:Intracellular Membranes / Q000201:enzymology* / Q000648:ultrastructure; D007527:Isoenzymes / Q000737:chemistry* / Q000378:metabolism; D008928:Mitochondria / Q000201:enzymology; D008961:Models, Structural
chemical_list: D007527:Isoenzymes; D003577:Cytochrome P-450 Enzyme System