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阐明脂肪酶的结构-机制关系:预测和改造催化特性的前景。

Elucidating structure-mechanism relationships in lipases: prospects for predicting and engineering catalytic properties.

作者信息

Kazlauskas R J

机构信息

Department of Chemistry, McGill University, Montréal, Québec, Canada.

出版信息

Trends Biotechnol. 1994 Nov;12(11):464-72. doi: 10.1016/0167-7799(94)90022-1.

DOI:10.1016/0167-7799(94)90022-1
PMID:7765546
Abstract

Organic chemists use lipases as catalysts in the synthesis of enantiomerically pure intermediates, to modify triglycerides, and to deprotect synthetic intermediates under mild conditions. They discovered most of these uses empirically, but the recent determination of the X-ray crystal structures of transition-state analogs bound to lipases may change this approach. These structures identified distinct binding regions for the acyl and alcohol portions of esters and suggested molecular-level explanations for the known enantiopreferences of lipases. In future, these structures may enable biotechnologists to design new substrates and reactions using molecular modeling, as well as to modify the activity and selectivity of lipases using site-directed mutagenesis.

摘要

有机化学家将脂肪酶用作合成对映体纯中间体、修饰甘油三酯以及在温和条件下使合成中间体脱保护的催化剂。他们大多是凭经验发现这些用途的,但最近对与脂肪酶结合的过渡态类似物的X射线晶体结构的测定可能会改变这种方法。这些结构确定了酯的酰基和醇部分的不同结合区域,并为脂肪酶已知的对映体选择性提供了分子层面的解释。未来,这些结构可能使生物技术人员能够利用分子建模设计新的底物和反应,以及利用定点诱变改变脂肪酶的活性和选择性。

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