Enantioselective Inhibition and Activation Allosteric Effects

The addition of small molecules has been shown to change the enantioselectivity of certain enzyme-catalyzed reactions. It is believed that such molecules bind to a site in the protein different from the active site, which leads to a conformational change in the active site. Such enzymes are called allosteric enzymes, i.e. enzymes that comprise of multiple subunits and multiple active sites. Binding of a cosubstrate or small molecule may cause an increase or decrease in the activity or selectivity of the enzyme. 

Since enantiomer selectivity, the f -value, is the ratio of the reaction rate with the two enantiomers either an allosteric increase in the reaction rate with one enantiomer or an allosteric decrease in the reaction rate with the other disfavored one will lead to an increase in E. 

Kinetic experiments may be used for revealing the type of inhibition in enzymes. By inserting experimental data to the inverted Michaelis-Menten equation this gives straight-line plots (Lineweaver-Burk), which can be extrapolated to yield the characterizing constants of the enzyme. However, the Michaelis-Menten model cannot account properly for the kinetic properties of allosteric enzymes [34]. 

Kinetic studies of the inhibitory effect of 1-butanol in different solvents on CALB have been performed and the competitive inhibition constant fQ values obtained correlated with the calculated activity coefficients of the substrate, suggesting that desolvation of the alcohol was the changing condition [35]. 

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