A Three-dimensional Model of Lanosterol 14alpha-demethylase of Candida albicans.

The three-dimensional structure of lanosterol 14alpha demethylase (P450(14DM), P450(51() of Candida albicans was modeled based on crystallographic coordinates of four prokaryotic cytochrome P450(S): P450BM3, P450cam, P450terp and P450eryF. The sequence of P450(51) was aligned to those of known proteins using a knowledge-based alignment method. The main chain coordinates of the structurally conserved regions (SCRs)) were transferred directly from the corresponding coordinates of P450BM3. The side chain conformations of SCRs) were determined based on the equivalent residues of four crystal structures which had the highest homologous scores. The model was then refined using molecular mechanics and molecular dynamics.The rationale of the resulting model were validated by Ramachandran plot,Profile-3K and hydropathy plot analysis. The structure-functionally important residues, such as the heme binding residues, the residues interacting with redox-partner protein and/or involved in electron transfer, the residues lining substrate access channel and the substrate binding residues, were identified from the model. These residues are candidates for further site-directed mutagensis and site-specific antipeptide antibody binding experiments.