Molecular Modeling Of CYP51 And Genome Analysis From Magnaporthe Grisea

Magnaporthe grisea is one of the most destructive fungal pathogen of rice and a model organism for studying plant-pathogen interaction. M. grisea Sterol 14a-demethylase (MgCYP51), a prime enzyme in membrane sterol biosynthesis, is a key target of antifungal drugs for rice blast. Compiling the potential gene products, identify their functions present in the pathogen and absent in the host by analyzing complete genomes, is now possible, for the genome sequence of the pathogen M. oryzae and the host Oryza sativa is now available.In this paper, the homology modeling and molecular docking methods were used to study the three-dimensional model structure of MgCYP51 and the binding modes of the activate center with fungicides. From the results of molecular modeling, the actives site structure and certain key residues responsible for inhibitor binding were identified. We used comparative metabolic pathway method to identify potential drug-target enzymes in M. oryzae which was non-homologous to host O. sativa and may be essential for pathogen’s survival as well as its growth for the emergence of multidrug-resistant called for an urgency to develop new drugs for rice blast.Comparison of the model with the template clearly showed that the MgCYP51 has similar features as the published crystal structure, and a direct comparison could be made. By molecular docking it was found that within the active site the residues Tyr112, Tyr493 and Met496 formed one large hydrophobic cavity while Lys137 formed the other region. Therefore hydrophobic substitutes of the ligands would be preferred when binding to these cavities. The residues Thr301, Ala305 and Ser309 formed one hydrophilic cavity where the N-4 of the triazole ring was bound to heme iron, and Tyr126 is the key residue of the other hydrophilic region.Comparative metabolic pathway analysis of the host and the pathogen showed that there were 7 metabolic pathways unique to M. grisea as D-Arginine and D-ornithine metabolism, methane metabolism, various types of N-glycan biosynthesis, other types of O-glycan biosynthesis, MAPK signaling pathway, cell cycle, meiosis. A systematic evaluation of metabolic pathways of host and pathogen locate 113 potential drug targets and can be extended to other pathogens in agricultural interest. Furthermore, We found 91 deficiencies in fatty acid metabolism, pyrimidine metabolism, P-alanine metabolism, amino sugar and nucleotide sugar metabolism, glycerylphosphatide metabolism, pantothenate and CoA biosynthesis, aminoacyl-tRNA biosynthesis. All this approach makes a rapid and effective potential drug target location possible, thereby promoting further investigation between host and pathogen.