The Reaction Mechanism of Bovine Lens Leucine Aminopeptidase

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.

本项研究采用量子力学/分子力学（QM/MM）方法，以AM1哈密顿量和灵活的分子力学部分对牛晶状体亮氨酸氨基肽酶（blLAP）的作用机理进行了研究。blLAP是一种细胞质外肽酶，催化肽链N端酰胺键的裂解。尽管基于晶体学数据的若干推测已经提出，但该普遍存在的酶的反应机制尚未得到完全阐明。在所调查的几种可能性中，一种路径被发现明显最为有利，并与实验结果高度一致。除了阐明活性位点残基的功能作用外，还对环境效应进行了评估。