受容体P450構造に基づいたアゾール系殺菌剤の構造活性相関　～受容体の３Ｄモデリングとメトコナゾールとの相互作用～

抄録

We have reported the quantitative structure-activity relationships of metconazole-related triazolylmethylcyclopentanols, and proposed the interaction mode between the triazolylmethylcyclopentanols and cytochlome P450 14 alpha demethylase (CYP51). The crystal structure of CYP51 from Mycobacterium tuberculosis (MTCYP51) was reported by Podust et al. this year. Active site model of phytopathogen's CYP51 is constructed by homology modeling based on MTCYP51 structure. The complex model structure of CYP51 from Botrytis cinerea with metconazole corresponds to our predicted interaction mode. 4-Chlolo-penyl group in metconazole makes nonbonded contacts with hydrophobic amino acid residues, PHE130, LEU143 and PHE149. Dimethyl group on cyclopentanol contacts hydrophobic amino acid residues, TYR122, LEU125, ILE375 and PHE508. LEU125 and MET308 closely contact cyclopentanol ring. Hydroxyl group of metconazole forms a hydrogen bond with TYR122 through a water molecule.