Homology modeling, molecular docking and spectra assay studies of sterol 14α-demethylase from Penicillium digitatum

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• 作者：Shuxiang Li (1)
  Jianhua Zhang (1)
  Shufen Cao (1)
  Rui Han (12)
  Yongze Yuan (1)
  Jiangke Yang (3)
  Yunjun Yan (3)
  Deli Liu (1) deliliu2002@yahoo.com.cn
• 关键词：Binding spectra – Homology modeling – Molecular docking – Penicillium digitatum – Sterol 14α ; demethylase
• 刊名：Biotechnology Letters
• 出版年：2011
• 出版时间：October 2011
• 年：2011
• 卷：33
• 期：10
• 页码：2005-2011
• 全文大小：2.0 MB
• 参考文献：1. Chen C-K, Leung SSF, Guilbert C et al (2010) Structural characterization of CYP51 from Trypanosoma cruzi and Trypanosoma brucei bound to the antifungal drugs posaconazole and fluconazole. PLoS Negl Trop Dis 4:e651
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  17. Strushkevich N, Usanov SA, Park HW (2010) Structural basis of human CYP51 inhibition by antifungal azoles. J Mol Biol 397:1067–1078
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  19. Zhang QY, Li DL, Wei P et al (2010) Structure-based rational screening of novel hit compounds with structural diversity for cytochrome p450 sterol 14α-demethylase from Penicillium digitatum. J Chem Inf Model 50:317–325
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• 作者单位：1. Hubei Key Laboratory of Genetic Regulation and Integrative Biology, College of Life Science, Central China Normal University, No. 152 Luo-Yu Road, Wuhan, 430079 People’s Republic of China2. Institute of Horticulture Qinghai Academy of Agriculture & Forestry, Qinghai University, Xining, 810016 People’s Republic of China3. College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430079 People’s Republic of China
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Life Sciences
  Microbiology
  Biotechnology
  Applied Microbiology
  Biochemistry
  
• 出版者：Springer Netherlands
• ISSN：1573-6776

文摘

Sterol 14α-demethylase from Penicillium digitatum (PdCYP51) is a prime target of antifungal drugs for citrus disease in plants. To design novel antifungal compounds, a homology model of PdCYP51 was constructed using the recently reported crystal structure of human CYP51 as the template. Molecular docking was performed to investigate the interaction of four commercial fungicides with the modeled enzyme. The side chain of these compounds interplayed with PdCYP51 mainly through hydrophobic and van der Waals interactions. Biochemical spectra analysis of inhibitors combined with PdCYP51 are also compatible with the docking results. This is the first molecular modeling for PdCYP51 based on the eukaryotic crystal structure of CYP51. The structural information and binding site mapping of PdCYP51 for different inhibitors obtained from this study could aid in screening and designing new antifungal compounds targeting this enzyme.