HOMOLOGY MODELING AND SUBSTRATE BINDING STUDY OF HUMAN KYNURENINE AMINOTRANSFERASE III

Abstract

Kynurenine aminotransferase III (KAT III) is a novel member of the kynurenine aminotransferase enzyme family. Its active site topology and structure characteristics have not been established. In this study, with extensive computational simulations, including homology modeling and molecular dynamics simulations, a 3D structure model of human KAT III dimer was created and refined. Furthermore, CDOCKER approach was employed to dock two ligands (L-methionine and L-tryptophan) into the active sites of human KAT III dimer and uncover the ligand-binding modes. The complexes were subjected to 5 ns MD simulation, and the results indicate that TYR119 and TRP13 might be the key residues as they have the large contributions to the binding affinity, which is in good agreement with the experimental results. Moreover, another two residues (ASP120 and TYR57) are also found that their strong interactions stabilize the whole system. The structural and biochemical insights obtained from the present study will be helpful for designing the specific inhibitors of human KAT III.