HOMOLOGY MODELING AND SUBSTRATE BINDING STUDY OF HUMAN KYNURENINE AMINOTRANSFERASE III
HOMOLOGY MODELING AND SUBSTRATE BINDING STUDY OF HUMAN KYNURENINE AMINOTRANSFERASE III
复制标题
人犬尿氨酸氨基转移酶III的同源建模和底物结合研究
DOI：
10.1142/s0219633612500587
复制
发表时间：
2012-07
影响因子：
2.4
通讯作者：
Sun, Chia-Chung
中科院分区：
文献类型：
--
作者：
Xu, Yu;Zheng, Qing-Chuan;Zhang, Hong-Xing;Sun, Chia-Chung
犬尿氨酸氨基转移酶III（KAT III）是犬尿氨酸氨基转移酶家族的新成员。其活性中心拓扑结构和结构特征尚未确定。在这项研究中，广泛的计算模拟，包括同源建模和分子动力学模拟，人KAT III二聚体的三维结构模型的创建和完善。此外，采用CDOCKER方法将两个配体（L-蛋氨酸和L-色氨酸）对接到人KAT III二聚体的活性位点，并揭示配体结合模式。对复合物进行了5 ns的分子动力学模拟，结果表明TYR 119和TRP 13可能是关键残基，因为它们对结合亲和力的贡献较大，这与实验结果吻合较好。另外两个残基（ASP 120和TYR 57）也被发现具有较强的相互作用，使整个系统稳定。从本研究中获得的结构和生物化学的见解将有助于设计特异性抑制剂的人KAT III。
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.
登录
查看更多内容
影响因子：
5.5
作者：
Hess, Berk;Kutzner, Carsten;Lindahl, Erik
通讯作者：
Lindahl, Erik
影响因子：
4.2
作者：
P. Guidetti;E. Okuno;R. Schwarcz
通讯作者：
P. Guidetti;E. Okuno;R. Schwarcz
影响因子：
2.5
作者：
Erhardt, S;Blennow, K;Engberg, G
通讯作者：
Engberg, G
影响因子：
3
作者：
Oostenbrink, C;Villa, A;Van Gunsteren, WF
通讯作者：
Van Gunsteren, WF
DOI：
10.1073/pnas.33.6.155
发表时间：
1947-01-01
影响因子：
11.1
作者：
BEADLE, GW;MITCHELL, HK;NYC, JF
通讯作者：
NYC, JF