A structure-controlled investigation of lipase enantioselectivity by a path-planning approach

被引：32

作者：

Guieysse, David ^{[2
]}

Cortes, Juan ^{[1
]}

Puech-Guenot, Sophie ^{[2
]}

Barbe, Sophie ^{[2
]}

Lafaquiere, Vincent ^{[2
]}

Monsan, Pierre ^{[2
]}

Simeon, Thierry ^{[1
]}

Andre, Isabelle ^{[2
]}

Remaud-Simeon, Magali ^{[2
]}

机构：

[1] CNRS, LAAS, F-31077 Toulouse, France

[2] INSA, CNRS, INRA, UMR Ingn Syst Biol & Procedes 5504,UMR792, F-31400 Toulouse, France

来源：

CHEMBIOCHEM | 2008年 / 9卷 / 08期

关键词：

enantioselectivity; enzymatic resolution; lipases molecular modeling; substrate access/exit pathway;

D O I：

10.1002/cbic.200700548

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A novel approach based on efficient path-planning algorithms was applied to investigate the influence of substrate access on Burkholderia cepacia lipase enantioselectivity. The system studied was the transesterification of 2-substituted racemic acid derivatives catalysed by B. cepacia lipase. In silica data provided by this approach showed a fair qualitative agreement with experimental results, and hence the potential of this computational method for fast screening of racemates. In addition, a collision detector algorithm used during the pathway searches enabled the rapid identification of amino acid residues hindering the displacement of substrates along the deep, narrow active-site pocket of B. cepacia lipase and thus provided valuable information to guide the molecular engineering of lipase enantioselectivity.

引用

页码：1308 / 1317

页数：10

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