Chitinase Of Asian Corn Borer:3D Modeling And Screening For Its Potent Inhibitors

The insect chitinase, belonging to glycohydrolase 18 family, is required for chitin recycling and synthesis of new cuticles or peritrophic membranes. Its activity is directly related to the insect's growth and development. Therefore, a chitinase is considered to be an ideal target for environment friendly and highly efficient insecticides.Our lab has revealed the cDNA and the deduced amino acid sequence of the chitinase from Asian corn borer recently. In this work we applied this enzyme for its 3D modeling so as to virtual screen for its potent inhibitors. Based on homology analysis, this chitinase shares very high identity with other 18 family glycotransferases, in particular the very conserved catalytic regions. Here we chose the shortest sequence of its catalytic domain of chitinase was chosen for structural modeling based on the knowledge that the shorter the sequence, the more accurate the modeling result. The following is what we accomplished during this study:1) Homology analysis of the catalytic domain of chitinases in the PDB database indicated that this chitinase shared the highest similarity with the human chitotriosidase named 1HKK with identities of 40.7%, positivities of 59.6% and gaps of 6.4%. Thus the crystal structure of 1HKK was chosen as its structural model.2) The receptor selected from 5 resulted modelling structures for inhibitors by molecular dynamics optimalization using software involving ProCheck, Profile₃D/verify and Prosa2003 as well. The evaluation was monitored under 310K thermostats and aqueous environment.3) 76 potent inhibitors were finally obtained by superposing the well known and highly efficient chitinase inhibitor "allosamidin" to the receptor, monitoring the distance between the catalytic amino acid residues and the inhibitor to 5A|°, and two-round screening from the SPECS database containing 43,432 molecules.4) 5 compounds selected form 76 potent inhibitors were applied to evaluate their inhibitory activity to purified chitinase, the results showed that the molecules have different inhibitory activity to the chitinase.