How Substrate Solvation Contributes to the Enantioselectivity of Subtilisin toward Secondary Alcohols
- 13 August 2005
- journal article
- Published by American Chemical Society (ACS) in Journal of the American Chemical Society
- Vol. 127 (35), 12228-12229
- https://doi.org/10.1021/ja0528937
Abstract
The current rule to predict the enantiopreference of subtilisin toward secondary alcohols is based on the size of the substituents at the stereocenter and implies that the active site contains two differently sized pockets for these substituents. Several experiments are inconsistent with the current rule. First, the X-ray structures of subtilisin show there is only one pocket (the S1‘ pocket) approximately the size of a phenyl group to bind secondary alcohols. Second, the rule often predicts the incorrect enantiomer for reactions in water. To resolve these contradictions, we refine the current rule to show that subtilisin binds only one substituent of a secondary alcohol and leaves the other in solvent. To test this refined empirical rule, we show that the enantioselectivity of a series of secondary alcohols in water varied linearly with the difference in hydrophobicity (log P/P0) of the substituents. This hydrophobicity difference accounts for the solvation of one substituent in water.Keywords
This publication has 18 references indexed in Scilit:
- Mirror-Image Packing in Enantiomer Discrimination: Molecular Basis for the Enantioselectivity of B.cepacia Lipase toward 2-Methyl-3-Phenyl-1-PropanolCell Chemical Biology, 2005
- Unexpected Subtilisin-Catalyzed Hydrolysis of a Sulfinamide Bond in Preference to a Carboxamide Bond in N-Acyl SulfinamidesJournal of the American Chemical Society, 2005
- Proteases Universally Recognize Beta Strands In Their Active SitesChemical Reviews, 2005
- Subtilisin-Catalyzed Resolution of N-Acyl ArylsulfinamidesJournal of the American Chemical Society, 2005
- The crystal structure of an autoprocessed Ser221Cys-subtilisin E-propeptide complex at 2.0 å resolutionJournal of Molecular Biology, 1998
- Probing Enzymic Transition State HydrophobicitiesBiochemistry, 1995
- Enzymatic Resolutions of Heterocyclic AlcoholsBiocatalysis, 1994
- Control of enzyme enantioselectivity by the reaction mediumJournal of the American Chemical Society, 1988
- Incorporation of D-amino acids into peptides via enzymic condensation in organic solventsJournal of the American Chemical Society, 1987
- Quantitative analyses of biochemical kinetic resolutions of enantiomersJournal of the American Chemical Society, 1982