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.

本报告呈现了一项基于 AM1 哈密顿量和柔性 MM 部分的量子力学/分子力学（QM/MM）研究，旨在探究牛晶状体赖氨酸氨基肽酶（blLAP）的作用机制。blLAP 是一种细胞质外肽酶，催化肽链N端酰胺键的裂解。尽管基于晶体结构数据已有一些推测，但该酶普遍存在的反应机理尚未完全阐明。在所研究的多种可能性中，一种路径被证明是最为有利且与实验结果高度吻合。此外，本研究还揭示了活性位点残基的功能作用，并对环境效应进行了估算。