Molecular rules for chemo- and regio-selectivity of Candida antarctica lipase B in peptide acylation reactions

• Published in: Journal of Molecular Catalysis B: Enzymatic
• Main Authors: Ferrari, Florent, Paris, Cedric, Maigret, Bernard, Bidouil, Christelle, Delaunay, Stéphane, Humeau, Catherine, Chevalot, Isabelle
• Other Authors: Laboratoire Réactions et Génie des Procédés (LRGP), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Ingénierie des Biomolécules (LIBio), Université de Lorraine (UL), Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)
• Format: Article in Journal/Newspaper
• Language: English
• Published: HAL CCSD 2014
• Subjects: [SDV]Life Sciences [q-bio]; Antarc*; Antarctica
• Online Access: https://hal.science/hal-01273453; https://doi.org/10.1016/j.molcatb.2013.12.007

International audience The chemo- and regio-selectivity of the lipase B of Candida antarctica (CALB) in peptide acylation by oleic acid was investigated combining experimental and theoretical methodologies. Molecular dynamics and docking simulations were performed to study the selectivity of CALB toward the dipeptide Lysine-Serine at the molecular level. To this end, a model that mimics the acyl-enzyme system was built from CALB crystallographic structure and optimized then to be used as docking target. One main orientation of the peptide within the catalytic cavity was obtained. The lysine side chain was observed to enter the cavity, placing the s-amino group as to be acylated near the catalytic residues. This result was consistent with the N-acylation experimentally observed, showing the robustness of the model. Docking simulations were then applied to the peptides Lysine-Tyrosine-Serine, Serine-Tyrosine-Lysine and Leucine-GlutamineLysine-Tryptophan aiming to predict the selectivity of the reaction. Whatever the peptidic sequence and its constitutive amino acids, the models suggested the preferential N-acylation of the lysine side chain. These theoretical results were in perfect accordance with experimental data showing that Ns-oleoyl-Lys derivatives were the major products.