A molecular dynamics and computational study of human KAT3 involved in KYN pathway

作者：Xu Yu; Zheng QingChuan^*; Yu LiYing; Zhang HongXing; Sun ChiaChung

来源：Science China Chemistry, 2013, 56(4): 514-523.

DOI：10.1007/s11426-012-4802-8

• kynurenine (KYN)
• kynurenine aminotransferases (KATs)
• pi-pi interaction
• molecular dynamic (MD) simulation
• interaction energy

Kynurenine aminotransferases (KATs) catalyze the transamination of kynurenine (KYN) pathway and endogenous KYNs have been suggested to highly correlate to abnormal brain diseases. HKAT3 is a key member of KAT family, while the binding mechanism of KYN and cofactor with HKAT3 has not been determined yet. In this study, we focus on the structure-function relationship among KYN, cofactor and HKAT3. The binding models of KYN complex and KYN&cofactor complex were obtained and were studied by molecular dynamics (MD) simulations. We identified several critical residues and influence of conformational changes in human kynurenine aminotransferase 3 (HKAT3) complexes. The cofactor may contribute largely not only to the catalysis, but also to the binding. In addition, a hypothesis is proposed that a strong hydrophobic interaction between Tyr159 and Lys280 may influence the binding mode and the binding region of the substrate and the cofactor. Our results will be a good starting point for further determination of the biological role.

• 出版日期2013-4
• 单位吉林大学