Molecular recognition, particularly enantiomeric specificity of biological molecules is a key consideration in designing drugs, pharmaceutical intermediate and in industrial production of chirally active intermediate. Although the molecular bases of many enzymes stereospecificity are not completely delineated, a number of protein engineering studies were able to enhance and even in some cases invert the stereospecificity of various enzymes. Herein, we review the current understanding on enzymes stereospecificity, and the effects of mutations to the stereospecific pockets due to enzymes engineering to improve stereospecificity.

Determining the molecular basis for stereospecificity of an enzyme requires the identification of the reacting orientations for both fastand slow-reacting substrate enantiomers [3]. The differences between the two orientations along with the accompanying interactions essentially form the molecular basis for the stereospecificity of enzymes. Identifying the reacting orientation for the fast-reacting enantiomer is straightforward; because the reacting atoms of the substrate are oriented in a way that they will best interact with the active site residues, whereas the non-reacting substrate moiety is positioned in the most fitted complementary pocket nearby.

Hence, the enantiomeric excess (e.e, %) of the correctly positioned or fast-reacting substrate would in turn, be higher than that of the slow-reacting counterpart. In such cases, the fast reacting substrate enantiomer that an enzyme preferentially catalyses would register a percentage e.e that approaches 100 [8]. Conversely, due to possibilities of compromises, orienting the slow-reacting substrate enantiomer to is often less straightforward. In some instances, certain features in the fast-reacting enantiomer will clash with the slow-reacting enantiomer within the tight active site pocket, as the two enantiomers are mirror images of each other. Therefore the difficulty in identifying the molecular basis of enzyme stereospecificity emanated from orienting the slow-reacting enantiomer [3].

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Lucy Morgan
Editorial Coordinator
Journal of Molecular Sciences
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