A structure-controlled investigation of lipase enantioselectivity by a path-planning approach.
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 silico 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.
Guieysse
David
D
UMR5504, UMR792 Ingénierie des Systèmes Biologiques et des Procédés, CNRS, INRA, INSA, 31400 Toulouse, France.
Cortés
Juan
J
Puech-Guenot
Sophie
S
Barbe
Sophie
S
Lafaquière
Vincent
V
Monsan
Pierre
P
Siméon
Thierry
T
André
Isabelle
I
Remaud-Siméon
Magali
M
D016956:Burkholderia cepacia / Q000201:enzymology*; D019295:Computational Biology; D008049:Lipase / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D015394:Molecular Structure; D013237:Stereoisomerism; D013379:Substrate Specificity
D008049:Lipase