Cytochrome P450 52A3: Modelling of 3D structure and surface mutations

Earlier W.-H. Schunck et al. [1] have prepared a water soluble enzymaticall y active fragment of cytochrome P450 52A3 (CYP52A3) which is lack of 66 ami no acid residues, existed as a dimer in aqueous solution. Now we propose 3D structure of the fragment, which is based on multiple sequence alignment o f the CYP52A3 with its homologues proteins of known 3D structure: CYP101, 1 02, 107A1 and 108. The structural model have been optimised and used as a p rototype for computer simulation of point mutations. These mutations should bring some changes in the surface properties. interfering dimer formation. For this aim the point of 22 hydrophobic amino acid residues have been seq uentially replaced with that of charged amino acids (GLU, ASP, ARG and LYS) . The scoring of "mutants" was conducted based on the changes of protein su rface hydrophobicity and protein-solvent interaction energy. An analy sis o f the surface hydrophobicity and protein-solvent interactions permit to sel ect most sensitive three sites (171, 352 and particularly 164 amino acid re sidues). The dimerization of the following "mutant" fragments must be inves tigated experimentally.