A molecular modelling study to rationalize the regioselectivity in acylation of flavonoïd glycosides catalysed by Candida antartica lipase B

• Published in: Journal of Molecular Catalysis B: Enzymatic
• Main Authors: de Oliveira, Eduardo, Humeau, Catherine, Chebil, Latifa, Maia, Elaine, Dehez, François, Maigret, Bernard, Ghoul, Mohamed, Engasser, Jean-Marc
• Other Authors: Ecole Nationale Supérieure d'Agronomie et des Industries Alimentaires (ENSAIA), Université de Lorraine (UL), Centre de Recherches sur les Macromolécules Végétales (CERMAV), Université Joseph Fourier - Grenoble 1 (UJF)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS), Knowledge representation, reasonning (ORPAILLEUR), INRIA Lorraine, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Institut National de Recherche en Informatique et en Automatique (Inria)-Université Henri Poincaré - Nancy 1 (UHP)-Université Nancy 2-Institut National Polytechnique de Lorraine (INPL)-Centre National de la Recherche Scientifique (CNRS)-Université Henri Poincaré - Nancy 1 (UHP)-Université Nancy 2-Institut National Polytechnique de Lorraine (INPL)-Centre National de la Recherche Scientifique (CNRS)
• Format: Article in Journal/Newspaper
• Language: English
• Published: HAL CCSD 2009
• Subjects: Candida antarctica lipase B; Docking; Flavonoid acylation; Molecular modelling; Regioselectivity; [SDV.BBM]Life Sciences [q-bio]/Biochemistry; Molecular Biology; Antarc*; Antarctica; antartic*
• Online Access: https://inria.hal.science/inria-00435075; https://doi.org/10.1016/j.molcatb.2009.01.011

International audience The regioselective behaviour of the Candida antarctica lipase B (CALB) towards two flavonoid glycosides, rutin and isoquercitrin, in the acetylation reaction was investigated through molecular modelling. A protocol constituted by a Monte Carlo-based docking procedure and classical force fields calculations was applied to find probable binding modes of the substrates inside the catalytic cavity and optimize the corresponding complexes. The analysis of these complexes allowed identifying productive ones (that means, those able to lead to the formation of the ester product) according to three parameters: (1) protein distortion; (2) stability of hydrogen bond interactions with the oxyanion hole residues; (3) localization of hydroxyl groups with regard to the region comprised between the catalytic histidine and serine residues. Results showed that the aglycon part of both rutin and isoquercitrin was localized at the entrance of the binding pocket, stabilized by hydrogen bond and hydrophobic interactions. The sugar part of the flavonoidswas placed close to the pocket bottom. In particular, only the primary 6" -OH of the isoquercitrin glucose and the secondary 4'" -OH of the rutin rhamnosewere expected to be acetylated, as theywere the only ones to stabilize simultaneously near to the catalytic histidine and the acetate bound to the catalytic serine. These findings are in accordance with experimental data and give a suitable explanation, at an atomic level, of the regioselectivity of CALB in the flavonoid glycosides acetylation.