Enzymes in organic synthesis 50. Probing the dimensions of the large hydrophobic binding region of the active site of pig liver esterase using substituted aryl malonate substrates

The active site model reported recently for the synthetically useful enzyme pig liver esterase (PILE) permits the structural specificity and stereoselectivity of the enzyme to be interpreted and predicted for a wide range of substrates. The specifications of the dimensions of this model were based on the specificity data available at that time. In order to test the model further, and to delineate more accurately the dimensions of its large hydrophobic (HL) binding pocket, PLE-catalyzed hydrolyses of dimethyl ortho- and para-methyl-, ethyl-, isopropyl-, and tert-butylphenyl 2-methylmalonate substrates have been carried out. Each of these malonate diesters proved to be a good substrate of the enzyme. In every case, the pro-S ester group was hydrolyzed to give R-acid-ester products of 78->-97% ee. The results show that the initial volume specified for the HL pocket was too small to accommodate the larger aryl groups of this substrate series. A modified model with an appropriately enlarged HL region is presented. The sizes of the other binding pockets remain unchanged. © 1991.

Duke Scholars

Author Eric John Toone Chemistry