title: Molecular modelling studies of substrate binding to the lipase from Rhizomucor miehei.
abstract: Lipase enzymes have found increasingly widespread use, especially in biotransformation reactions in organic synthesis. Due to their efficiency and high enantioselectivity, they can be employed in a variety of reactions to carry out asymmetric hydrolyses, esterifications and transesterifications. However, the reasons for their stereospecificity have not been fully correlated with the enzyme structure. Employing molecular modelling techniques and existing experimental data, a transesterification reaction using Rhizomucor miehei lipase was studied. The results indicate that the major controlling factor for this reaction is hydrophobic in nature, providing support for previous literature hypotheses. In addition, computational experiments suggest that the origin of enantioselectivity is the formation of essential hydrogen bonds in and around the catalytic triad of active site residues. Only one enantiomer of the substrate is able to form these hydrogen bonds during the formation of the first tetrahedral transition state.
authors.affiliation: Department of Chemistry, Exeter University, U.K.
authors.forename: A T
authors.initials: AT
authors.lastname: Yagnik
authors.forename: J A
authors.initials: JA
authors.lastname: Littlechild
authors.forename: N J
authors.initials: NJ
authors.lastname: Turner
mesh_terms: D001665:Binding Sites; D002384:Catalysis; D003198:Computer Simulation; D004791:Enzyme Inhibitors / Q000737:chemistry; D006860:Hydrogen Bonding; D008024:Ligands; D008049:Lipase / Q000737:chemistry*; D008958:Models, Molecular; D009090:Mucorales / Q000201:enzymology*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013816:Thermodynamics; D014961:X-Ray Diffraction
chemical_list: D004791:Enzyme Inhibitors; D008024:Ligands; C093666:Lipozyme; D008049:Lipase