Structure-Activity Relationship of Azole Fungicide Based on the Crystal Structure of Cytochrome P450. - Homology Search of Cytochrome P450 14a-demethylase (CYP51) -

Abstract

Azole fungicides inhibit the activity of cytochrome P450 14a-demethylase (CYP51) in sterol biosynthesis. The three-demensional structures of CYP51 of Candida albicans have been modeled on the basis of crystal structure of other P450s, such as P450cam and P450BM3. We have proposed the active site of CYP51 and the binding mode for metconazole and ipconazole to CYP51 by QSAR analyses. In this paper, to confirm our predicted active site of CYP51, we model the 3-D structure of phytopathogen's CYP51 on the basis of crystal structure of CYP51 from Mycobacterium tuberculosis (MTCYP51), which was reported in this year. From amino acid sequence alignment between phytopathogen's CYP51 and MTCYP51, it is thought that homology modeling of CYP51 based on the structure of MTCYP51 is more accurate than that of P450cam or P450BM3.