Molecular Modelling Approaches for Designing Inhibitors of L-Amino Acid Oxidase from Crotalus adamanteus Venom

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 ischolar_main mean square deviations obtained from superposition of the FADbinding, 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-aminobenzoic 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 μM respectively.