title: Homology modeling and screening of new 14α-demethylase inhibitor (DMI) fungicides based on optimized expression of CYP51 from Ustilago maydis in Escherichia coli.
abstract: Ustilago maydis infection is a serious disease affecting corn crops worldwide. Sterol 14α-demethylase (CYP51) is one of the key enzymes of sterol biosynthesis and an effective target of antifungal drugs. To further study the interaction between CYP51 and drugs and exploit more specific 14α-demethylase inhibitor (DMI) fungicides for U. maydis, in this study homology modeling of CYP51 from U. maydis (UmCYP51) templated as the eukaryotic orthologues (the human CYP51) and screening of new DMI fungicides based on optimized expression were carried out for the first time. In addition, XF-113 and ZST-4 were screened by analyzing the spectral characteristics between the purified UmCYP51-35 and fungicides. These results provide a theoretical basis and new ideas for efficient design and development of new antifungal drugs.
authors.affiliation: Hubei Key Laboratory of Genetic Regulation and Integrative Biology, College of Life Science, Huazhong Normal University, Wuhan 430079, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Han
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhang
authors.forename: Shuxiang
authors.initials: S
authors.lastname: Li
authors.forename: Shufen
authors.initials: S
authors.lastname: Cao
authors.forename: Hui
authors.initials: H
authors.lastname: Geng
authors.forename: Yongze
authors.initials: Y
authors.lastname: Yuan
authors.forename: Wenjing
authors.initials: W
authors.lastname: Xiao
authors.forename: Shenghua
authors.initials: S
authors.lastname: Liu
authors.forename: Deli
authors.initials: D
authors.lastname: Liu
mesh_terms: D058888:14-alpha Demethylase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D000595:Amino Acid Sequence; D004353:Drug Evaluation, Preclinical; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D005659:Fungicides, Industrial / Q000737:chemistry* / Q000494:pharmacology; D015870:Gene Expression; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D016415:Sequence Alignment; D058886:Sterol 14-Demethylase / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D014588:Ustilago / Q000201:enzymology*
chemical_list: D058888:14-alpha Demethylase Inhibitors; D005656:Fungal Proteins; D005659:Fungicides, Industrial; D058886:Sterol 14-Demethylase