Three-point model

Fig. 5.20. Chiral crown ethers which have been used for chiral recognition studies with the ammonium ions in the inset. As a reference, the non-chiral crown at the center left was used. Bottom Three-point model for chiral recognition of ammonium ions in crown ethers (I = large, m = medium, s = small substituents).

More reeently, Mesecar and Koshland [32], following an investigation of the enzyme isoeitrate dehydrogenase, have found that the three-point model does not always hold. Examination of metal-free crystals of the enzyme strueture reveals that only the 25,37 -(L)-isocitrate binds, whereas in the presenee of magnesium ions only the 22 ,3iS -(D)-enantiomer binds. Examination of x-ray structures of the two enzyme-substrate complexes reveals three common binding sites for both enantiomeric substrates that differ at a fourth site. Based on their observations, the authors proposed that the three-point model is only applicable if the assumption is made that the substrate can approach a planar surface from one direction. Thus a fourth location, either a direction requirement or an additional binding site, is essential to distinguish between a pair of enantiomers (Fig. 5). 

Fig. 1. Three-point model of chiral discrimination. (A) The R-enantiomer is shown to be capable of three simultaneous interactions with the chiral selector and (B) the S-enantiomer is only capable of two simultaneous interactions (A-A and B-B ).

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