title: Structure and function of cytochromes P450: a comparative analysis of three crystal structures.
abstract: BACKGROUND
  Cytochromes P450 catalyze the oxidation of a variety of hydrophobic substrates. Sequence identities between P450 families are generally low (10-30%), and consequently, the structure-function correlations among P450s are not clear. The crystal structures of P450terp and the hemoprotein domain of P450BM-3 were recently determined, and are compared here with the previously available structure of P450cam.
  
  
  RESULTS
  The topology of all three enzymes is quite similar. The heme-binding core structure is well conserved, except for local differences in the I helices. The greatest variation is observed in the substrate-binding regions. The structural superposition of the proteins permits an improved sequence alignment of other P450s. The charge distribution in the three structures is similarly asymmetric and defines a molecular dipole.
  
  
  CONCLUSIONS
  Based on this comparison we believe that all P450s will be found to possess the same tertiary structure. The ability to precisely predict other P450 substrate-contact residues is limited by the extreme structural heterogeneity in the substrate-recognition regions. The central I-helix structures of P450terp and P450BM-3 suggest a role for helix-associated solvent molecules as a source of catalytic protons, distinct from the mechanism for P450cam. We suggest that the P450 molecular dipole might aid in both redox-partner docking and proton recruitment for catalysis.
authors.affiliation: Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas 75235-9050, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Hasemann
authors.forename: R G
authors.initials: RG
authors.lastname: Kurumbail
authors.forename: S S
authors.initials: SS
authors.lastname: Boddupalli
authors.forename: J A
authors.initials: JA
authors.lastname: Peterson
authors.forename: J
authors.initials: J
authors.lastname: Deisenhofer
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D003196:Computer Graphics; D018360:Crystallography, X-Ray; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid
chemical_list: D003577:Cytochrome P-450 Enzyme System