Naslov
QM/MM Study of the Burkholderia cepacia Lipase Catalyzed Secondary Alcohol Esterification

Autori
Tomić, Sanja ; Ceilinger, Igor ; Hodošček, Milan ; Janežić, Dušanka

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, ostalo

Izvornik
Book of Abstracts - The Conference on Molecular Simulations in Biosystems and Material Science / Nielabla, P. - Konstanz : Universitaet Konstanz, 2008, 92-92

Skup
The Conference on Molecular Simulations in Biosystems and Material Science

Mjesto i datum
Konstanz, Njemačka, 02.04.2008. - 05.04.2008

Vrsta sudjelovanja
Poster

Vrsta recenzije
Nije recenziran

Ključne riječi
lipase; reactions; enantioselectivity; QM/MM

Sažetak
Bacterial lipases are interesting for biotechnology because of their high enantioselectivity toward chemically and pharmaceutically important compounds. We studied the enantioselectivity of Burkholderia cepacia lipase toward secondary alcohol (R, S)-1-phenoxy-2-hydroxybutane (1) and its ester (E1). The goal of our study was to find out if the experimentally determined binding modes for the inhibitor1 (phosphonate analogue of E1) can be considered as productive ones. Namely, could the substrate bound in this way be chemically modified? Both inhibitor isomers, S and R bind into the BCL active site similarly ; however the H-bond between the alcohol oxygen and catalytic His286 in the case of R-inhibitor can be formed, and in the case of S-inhibitor can not. On the other hand molecular modelling for both, S and R- enantiomers of E1 revealed orientations in which all hydrogen bonds characteristic for productive binding are formed.2 Starting from the four covalent complexes with different orientation of the substrate, we modelled the ester (S and R E1) hydrolysis and the alcohol (S and R 1) esterification using quantum chemical3 (QM) and QM/MM methods. The calculations revealed that ester release is possible from all four covalent complexes. Alcohol release from the BCL-E1 complex in which the S-substrate is bound in the same manner as the S-inhibitor in the crystal structure however is not possible. The energy difference between the BCL complex with S-enantiomer of E1, determined by molecular modelling, and the complex with R-enantiomer of E1 (either modelled or crystallographic) is in agreement with the experimentally determined enantiomeric ratio.1

Izvorni jezik
Engleski

Znanstvena područja
Fizika

POVEZANOST RADA