Homology modeling of a novel epoxide hydrolase (EH)from Aspergillus niger SQ-6: structure-activity relationshipin expoxides inhibiting EH activity

摘要

The 3D structure of a novel epoxide hydrolasefrom Aspergillus niger SQ-6 (sqEH) was constructed byusing homology modeling and molecular dynamics simu-lations. Based on the 3D model, Asp191, His369 andG1u343 were predicted as catalytic triad. The putative activepocket is a hydrophobic environment and is rich in someimportant non—polar residues (Pro318, Trp282, Pro319,Pro317 and Phe242). Using three sets of epoxide inhibitorsfor docking study, the interaction energies of sqEH with eachinhibitor are consistent with their inhibitory effects inprevious experiments. Moreover, a critical water moleculewhich closes to the His369 was identified to be an idealposition for the hydrolysis step of the reaction. Two tyrosineresidues (Tyr249 and Tyr312) are able to form hydrogenbonds with the epoxide oxygen atom to maintain the initialbinding and positioning of the substrate in the active pocket.These docked complex models can well interpret thesubstrate specificity of sqEH, which could be relevant forthe structural—based design of specific epoxide inhibitors.