title: Identification and location of alpha-helices in mammalian cytochromes P450.
abstract: A model of the alpha-helical structure of mammalian cytochromes P450 is proposed. The location and sequence of alpha-helices in mammalian cytochromes P450 were predicted from their homology with those of cytochrome P450cam, and these sequences were generally confirmed as helical in nature by using a secondary structure prediction method. These analyses were applied to 26 sequences in 6 gene families of cytochrome P450. Mammalian cytochromes P450 consist of approximately 100 amino acid residues more than cytochrome P450cam. This difference was accounted for by three major areas of insertion: (1) at the N-terminus, (2) between helices C and D and between helices D and E, and (3) between helices J and K. Insertion 1 has been suggested by others as a membrane anchoring sequence, but the apparent insertions at 2 and 3 are novel observations; it is suggested that they may be involved in the binding of cytochrome P450 reductase. Only the mitochondrial cytochrome P450 family appeared to show a major variation from this pattern, as insertion 2 was absent, replaced by an insertion between helices G and H and between helices H and I. This may reflect the difference in electron donor proteins that bind to members of this cytochrome P450 family. Other than these differences the model of mammalian cytochromes P450 proposed maintains the general structure of cytochrome P450cam as determined by its alpha-helical composition.
authors.affiliation: Department of Clinical Pharmacology, Royal Postgraduate Medical School, London, U.K.
authors.forename: R J
authors.initials: RJ
authors.lastname: Edwards
authors.forename: B P
authors.initials: BP
authors.lastname: Murray
authors.forename: A R
authors.initials: AR
authors.lastname: Boobis
authors.forename: D S
authors.initials: DS
authors.lastname: Davies
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005796:Genes; D008969:Molecular Sequence Data; D005810:Multigene Family; D011487:Protein Conformation; D012689:Sequence Homology, Nucleic Acid
chemical_list: D003577:Cytochrome P-450 Enzyme System