Molecular modelling approaches for designing inhibitors of L-amino acid oxidase from Crotalus adamanteus venom

摘要

L-amino acid oxidase (LAAO) from snake venom induces diverse toxicity into the victims, which is attributed to H2O2 generated during the catalytic conversion of L-amino acids. In this study, homology model of LAAO from Crotalus adamanteus has been compared with the crystal structure of LAAO from Calloselasma rhodostoma. The root mean square deviations obtained from superposition of the FAD-binding, substrate-binding and helical domains of LAAO from Crotalus adamanteus with those of LAAO from Calloselasma rhodostoma crystal structure confirmed a high degree of structural similarity between them. Based on the interactions of the substrate, L-phenylalanine and the reversible inhibitor, o-amino-benzoic acid with the catalytic residues of LAAO from Calloselasma rhodostoma, five probable inhibitors were designed. AutoDock Vina program was employed to perform automated molecular docking of these probable inhibitors. Two of them emerged as reversible inhibitors with IC50 values of 1.6 and 3.3 mu M respectively.