title: Expression and homology modelling of sterol 14alpha-demethylase of Magnaporthe grisea and its interaction with azoles.
abstract: BACKGROUND
  Magnaporthe grisea (Hebert) ME Barr infection is one of the most serious diseases for cultivated rice in the world. Sterol 14alpha-demethylase (CYP51) is an important drug target for microbial pathogenic infections. To exploit specific and effective fungicides for M. grisea better, the authors have analysed the characteristics of interaction between sterol 14alpha-demethylase from M. grisea (MGCYP51) and azoles. MGCYP51 with truncation of N-terminal residues was cloned and expressed in E. coli, difference binding spectra of MGCYP51 induced by addition of four commercial azoles were determined and molecular modelling of MGCYP51 based on the crystal structure of Mycobacterium tuberculosis Lehmann & Newman and docking with the azoles were performed.
  
  
  RESULTS
  The affinity of the azoles for MGCYP51 was positively correlated with their hydrophobicity. Amino acid residues Tyr112, Phe120, Phe220, His308 and Phe497 of MGCYP51, forming a large hydrophobic cavity, are the key residues interacting with azole fungicides. Furthermore, Phe220 and Phe497 are fungus and species specific respectively.
  
  
  CONCLUSIONS
  The results suggest that the more potent azole fungicides for MGCYP51 should possess more hydrophobic groups interacting with residues Phe220 and Phe497.
authors.affiliation: College of Life Science, Central China Normal University, Wuhan, PR China.
authors.forename: Jiaoyan
authors.initials: J
authors.lastname: Yang
authors.forename: Qingye
authors.initials: Q
authors.lastname: Zhang
authors.forename: Mingjun
authors.initials: M
authors.lastname: Liao
authors.forename: Min
authors.initials: M
authors.lastname: Xiao
authors.forename: Wenjing
authors.initials: W
authors.lastname: Xiao
authors.forename: Shao
authors.initials: S
authors.lastname: Yang
authors.forename: Jian
authors.initials: J
authors.lastname: Wan
mesh_terms: D000596:Amino Acids; D001393:Azoles / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D001665:Binding Sites; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005656:Fungal Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D005659:Fungicides, Industrial / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D015870:Gene Expression; D057927:Hydrophobic and Hydrophilic Interactions; D020082:Magnaporthe / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D012275:Oryza / Q000382:microbiology; D010935:Plant Diseases / Q000382:microbiology; D011485:Protein Binding; D016415:Sequence Alignment; D058886:Sterol 14-Demethylase
chemical_list: D000596:Amino Acids; D001393:Azoles; D005656:Fungal Proteins; D005659:Fungicides, Industrial; D003577:Cytochrome P-450 Enzyme System; D058886:Sterol 14-Demethylase