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The sequence homologies of cytochromes P-450 and active-site geometries

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Summary

The amino acid sequence alignment of 16 cytochrome P-450 proteins representative of the major families is reported. The sequence matching process has been carried out on the basis of maximum homology by residue type, retention of secondary structure and minimization of deletions/insertions except where additional loop regions exist. From the starting point of known reported sequence homology matching from the literature, a realignment on the basis of conserved residues involved in both structure and function gives rise to a self-consistent set of sequences which correlates with known mechanistic and structural data. Once fitted, these archetypal sequences form a straightforward template for the alignment of all P-450 subfamilies. Computer modelling of the active-site regions constructed from homology with the bacterial form of the enzyme (P-450CAM) evinces the correct substrate specificity. Furthermore, the construction of the macromolecular assembly of components of the cytochrome P-450 system on the microsomal endoplasmic reticular membrane is presented from the evidence of site-directed mutagenesis, analysis by molecular probes, X-ray crystallography and molecular modelling.

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Authors and Affiliations

  1. Department of Biochemistry, University of Surrey, GU2 5XH, Guildford, Surrey, U.K.

    David F. V. Lewis

  2. Department of Theoretical Medicinal Chemistry, Janssen Research Foundation, B-2340, Beerse, Belgium

    Henri Moereels

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  1. David F. V. Lewis
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Lewis, D.F.V., Moereels, H. The sequence homologies of cytochromes P-450 and active-site geometries. J Computer-Aided Mol Des 6, 235–252 (1992). https://doi.org/10.1007/BF00123379

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