Comparative Studies on Crystal Structures of Four Members of Cytochrome P450 Superfamily.

Secondary and steric structures and hydropathy plots of the 4 crystals of P450cam, P450terp, P450eryF and P450BM3 were compared to illustrate the structural conservation of cytochrome P450 superfamily proteins. Although sequence identities of four P450s are generally low (19%-26%), their topology is quite similar. All four structures have 13 alpha-helices and beta1-beta4 sheets in common. Four crystal structures were superimpossed by root-mean-square (RMS) fit of the prophyrin ring carbon atoms of prosthetic group heme to obtain the structure-based sequence alignment of four proteins. The RMS deviations of Calpha distance of each motifs were analyzed by hierarchical cluster analysis. The structural subsets were divided into four categories of structural conservation: the most conserved region, the less conserved region, the less variable region and the variable region. The first two groups (56.9 percentage of the aligned positions that have no gaps) include all the interior structures and active site residues. All four P450 proteins have the common hydrophobic and hydrophilic segments by hydropathy plots analyses. All the comparison results of P450 protein crystal structures provided the basis for structure-based sequence alignment of cytochrome P450 proteins.