Schürer Gudrun, Horn Anselm H C, Gedeck Peter, Clark Timothy
Computer-Chemie-Centrum, Friedrich-Alexander-Universität Erlangen-Nürnberg, Nägelsbachstrasse 25, 91052 Erlangen, Germany, and Novartis Horsham Research Centre, Wimblehurst Road, Horsham, West Sussex RH12 5AB, U.K.
J Phys Chem B. 2002 Aug 29;106(34):8815-30. doi: 10.1021/jp025575s.
We present a quantum mechanical/molecular mechanical (QM/MM) study using the AM1 Hamiltonian and a flexible MM part on the mode of action of the bovine lens leucine aminopeptidase (blLAP), a cytosolic exopeptidase that catalyzes the cleavage of the N-terminal amide bond of peptides. The reaction mechanism of this ubiquitous enzyme has not yet been clarified completely, although some suggestions based on crystallographic data have been made. One path of the several possibilities investigated was found to be clearly the most favorable and in good agreement with experimental results. Besides the elucidation of the functional roles of active-site residues, an estimation of the environment effects is given.
我们采用AM1哈密顿量和灵活的分子力学部分，对牛晶状体亮氨酸氨肽酶（blLAP）的作用模式进行了量子力学/分子力学（QM/MM）研究。blLAP是一种胞质外肽酶，催化肽的N端酰胺键的裂解。尽管基于晶体学数据已经提出了一些建议，但这种普遍存在的酶的反应机制尚未完全阐明。在所研究的几种可能性中，发现其中一条路径明显是最有利的，并且与实验结果高度吻合。除了阐明活性位点残基的功能作用外，还给出了环境效应的估计。
