Theoretical study on 3-hydroxykynurenine transaminase by homology modeling and molecular dynamics

The three-dimensional (3D) model of the 3-hydroxykynurenine transaminase (3-HKT) is constructed based on the crystal structure of the alanine-glyoxylate aminotransferase (EC 2.6.1.44, PDB code 1VJO) by using InsightII/Homology module. With the aid of the molecular mechanics and molecular dynamics methods, the last refined model is obtained and further assessed by Profile-3D and ProStat, which confirm that the refined model is reliable. With this model, a flexible docking study is performed and the result indicates that Trp104 and Gln204 are important residues as they have strong hydrogen bonding interactions with 3-HK respectively and they will act as a vital role in catalysis of 3-HKT. The Trp104 is in good agreement with the experimental result by Li et al. From the docking studies, we also suggest that the residues of Lys205 and Pro211 in 3-HKT are two important determinant residues in binding as they have strong van der Waals contacts with the 3-HK. Our results may be helpful for further experimental investigations.