Zhao Yong-Shan, Zheng Qing-Chuan, Zhang Hong-Xing, Chu Hui-Ying, Sun Chia-Chung
State Key Laboratory of Theoretical and Computational Chemistry, Institute of Theoretical Chemistry, Jilin University, Changchun 130023, P. R. China.
J Mol Model. 2009 May;15(5):499-505. doi: 10.1007/s00894-008-0430-9. Epub 2008 Dec 16.
The three-dimensional (3D) model of the human acidic mammalian chitinase (hAMCase) was constructed based on the crystal structure of the human chitotriosidase (EC 3.2.1.44, PDB code 1HKK) by using InsightII/Homology module. With the aid of molecular mechanics and molecular dynamics methods, the last refined model was obtained and further assessed by Profile-3D and Procheck, which confirms that the refined model is reliable. Furthermore, the docking results of the ligands (allosamidin and NAG(2)) into the active site of hAMCase indicate that allosamidin is a more preferred ligand than NAG(2), and that Glu119 forms hydrogen bond with allosamidin, which is in good agreement with the experimental results. From the docking studies, we also suggest that Trp10, Glu49, Asp192, and Glu276 in hAMCase are four important determinant residues in binding as they have strong van-der-Waals and electrostatic interactions with the ligand, respectively.
基于人几丁质三糖酶（EC 3.2.1.44，PDB编号1HKK）的晶体结构，使用InsightII/同源性模块构建了人酸性哺乳动物几丁质酶（hAMCase）的三维（3D）模型。借助分子力学和分子动力学方法，获得了最终优化模型，并通过Profile-3D和Procheck进一步评估，证实优化后的模型是可靠的。此外，配体（别洛沙米定和NAG(2)）与人酸性哺乳动物几丁质酶活性位点的对接结果表明，别洛沙米定是比NAG(2)更合适的配体，并且Glu119与别洛沙米定形成氢键，这与实验结果高度吻合。从对接研究中，我们还表明，人酸性哺乳动物几丁质酶中的Trp10、Glu49、Asp192和Glu276是结合过程中的四个重要决定残基，因为它们分别与配体具有强烈的范德华力和静电相互作用。
