Molecular Basis for Empirical Rules that Predict the Stereoselectivity of Hydrolases

  • Alexandra N. E. Weissfloch
  • Romas J. Kazlauskas
Part of the NATO Science Partnership Sub-Series: 1: book series (ASDT, volume 33)

Abstract

Hydrolases are the most widely used enzymes for organic synthesis, both in academic laboratories and in commercial production. Most researchers focus on a few well-studied lipases and proteases. To predict the stereoselectivity of these ‘work horse’ hydrolases, researchers developed empirical rules or models. These empirical rules describe the shape and other features of either a good substrate (substrate model) or of the binding site (active site model). Researchers use these rules to design new syntheses using hydrolases. Recently, x-ray crystallographers have solved the three-dimensional structures of all the workhorse lipases, but these structures are too complex to use directly in the organic synthesis design. However, by combining the empirical rules with x-ray structures, one obtains a powerful and useful tool. The empirical rules identify the most important features of the substrate binding site (usually its size and shape) and thus simplify interpretation of the x-ray structures. On the other hand, the x-ray structures provide a molecular basis for the validity of the rules, add molecular details to the rules that explain puzzling features. This review summarizes recent efforts to combine both empirical rules and three-dimensional structures to rationally-design new applications of hydrolases in organic synthesis.

Keywords

Hydrolysis Amide Phenyl Serine Histidine 

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Copyright information

© Springer Science+Business Media Dordrecht 2000

Authors and Affiliations

  • Alexandra N. E. Weissfloch
    • 1
  • Romas J. Kazlauskas
    • 1
  1. 1.Department of ChemistryMcGill UniversityMontréalCanada

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