title: A structure-controlled investigation of lipase enantioselectivity by a path-planning approach.
abstract: 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.
authors.affiliation: UMR5504, UMR792 Ingénierie des Systèmes Biologiques et des Procédés, CNRS, INRA, INSA, 31400 Toulouse, France.
authors.forename: David
authors.initials: D
authors.lastname: Guieysse
authors.forename: Juan
authors.initials: J
authors.lastname: Cortés
authors.forename: Sophie
authors.initials: S
authors.lastname: Puech-Guenot
authors.forename: Sophie
authors.initials: S
authors.lastname: Barbe
authors.forename: Vincent
authors.initials: V
authors.lastname: Lafaquière
authors.forename: Pierre
authors.initials: P
authors.lastname: Monsan
authors.forename: Thierry
authors.initials: T
authors.lastname: Siméon
authors.forename: Isabelle
authors.initials: I
authors.lastname: André
authors.forename: Magali
authors.initials: M
authors.lastname: Remaud-Siméon
mesh_terms: 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
chemical_list: D008049:Lipase