engleski

Quantum Mechanical Study of Burkholderia cepacia Lipase Enantioselectivity

Quantum mechanical, semi-empirical (AM1) and ab initio (6-31G*) study of the Bukrholderia cepacia lipase (BCL) catalysed reactions of the secondary alcohol esterification and its ester hydrolysis is presented. We have selected BCL for our study because of numerous experimental results available, but also because of its broad selectivity and stability that makes it interesting for industrial use. Previously we developed models for predicting lipase stereroselectivity towards primary and secondary alcohols according to their structural parameters. In this work we show that experimentally determined binding modes should be taken with caution when modelling chemical reactions, i.e. the initial states for study of the lipase catalysed reactions should be carefully chosen. An important result is that only some of the experimentally determined binding modes are catalytically competent in the sense that chemical modification of the substrate is possible. For the rational enzyme engineering these binding modes are the most relevant. We also investigated the influence of the tetrahedral atom type, C and P, upon the energy barriers in the proton transfer reactions from the catalytic histidine (His286) to either the catalytic serine (Ser87) or the alcohol oxygen of the substrate.

lipase catalysis proton transfer; hydrolysis of secondary alcohol ester; esterification of secondary alcohol; Burkholderia cepacia lipase; quantum mechanical study; molecular modelling

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