Elucidating structure-mechanism relationships in lipases: prospects for predicting and engineering catalytic properties.
Organic chemists use lipases as catalysts in the synthesis of enantiomerically pure intermediates, to modify triglycerides, and to deprotect synthetic intermediates under mild conditions. They discovered most of these uses empirically, but the recent determination of the X-ray crystal structures of transition-state analogs bound to lipases may change this approach. These structures identified distinct binding regions for the acyl and alcohol portions of esters and suggested molecular-level explanations for the known enantiopreferences of lipases. In future, these structures may enable biotechnologists to design new substrates and reactions using molecular modeling, as well as to modify the activity and selectivity of lipases using site-directed mutagenesis.
Kazlauskas
R J
RJ
Department of Chemistry, McGill University, Montréal, Québec, Canada.
D000595:Amino Acid Sequence; D001665:Binding Sites; D001709:Biotechnology / Q000639:trends; D002384:Catalysis; D018360:Crystallography, X-Ray; D004950:Esterases / Q000378:metabolism; D006801:Humans; D008049:Lipase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015202:Protein Engineering; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D004950:Esterases; D008049:Lipase