title: Primary and secondary structural patterns in eukaryotic cytochrome P-450 families correspond to structures of the helix-rich domain of Pseudomonas putida cytochrome P-450cam. Indications for a similar overall topology.
abstract: An extensive sequence analysis of the eukaryotic cytochrome P-450 (P-450) protein families was conducted with a view to identifying conserved regions that might be related to secondary structural features in the Pseudomonas putida camphor hydroxylase (P-450cam). All sequences available on-line were collected, classified and aligned within families. Distinctively different sequences were chosen from each of seven eukaryotic families, and an unbiased multi-alignment was constructed. Profile patterns of the most conserved regions were generated and screened against the sequence of P-450cam, the structure of which has been elucidated by X-ray crystallography. While some of these profiles did not map on the P-450cam sequence, the structurally most important helices were clearly identified and the correlations were found to be statistically significant. Our analysis suggests that the helix-rich domain with the cysteine pocket and the oxygen-binding site is conserved in all P-450 forms. Helices I and L from P-450cam can be easily identified in all eukaryotic P-450 forms. Other helices which seem to exist in all P-450 forms include helices C, D, G and J. K. In the helix-poor domain of P-450cam, only structures b3/b4 seem to have been conserved. The obvious sequence conservation throughout the helix-rich domain of the P-450cam protein might be expected for a molecular class whose overall topology is preserved. Additional support for the conservation of structure between eukaryotic cytochromes P-450 and P-450cam comes from secondary structure prediction of the eukaryotic sequences.
authors.affiliation: Department of Molecular and Cell Biology, University of Aberdeen, Marischal College, Scotland.
authors.forename: C A
authors.initials: CA
authors.lastname: Ouzounis
authors.forename: W T
authors.initials: WT
authors.lastname: Melvin
mesh_terms: D000595:Amino Acid Sequence; D019475:Camphor 5-Monooxygenase; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D046911:Macromolecular Substances; D008297:Male; D006899:Mixed Function Oxygenases / Q000737:chemistry / Q000235:genetics*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011549:Pseudomonas / Q000201:enzymology*; D012689:Sequence Homology, Nucleic Acid
chemical_list: D046911:Macromolecular Substances; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D019475:Camphor 5-Monooxygenase