Stabilisation of Enolate Anions — The Enolase Superfamily

Yet another example of a family of Mg -dependent enzymes is the enolase superfamily which catalyse a series of mechanistically diverse and different overall reactions. However, they all share a partial reaction in which an active site base of the enzyme abstracts the a-proton of a carboxylate substrate to generate an enolate anion intermediate 

FIGURE 10.10 The substrates, enolate anion intermediates, and products of the MR MLE and enolase reactions. (Adapted from Gerlt, Babbitt, Rayment, 2005.) 

In enolase, the substrate, 2-phosphoglycerate (2-PGA) is coordinated to two Mg ions, one of which is liganded to the three conserved carboxylate residues (Asp 246, Glu 295, and Asp 320). Currently, more than 600 enolase sequences have been identified in the databases, and aU are thought to be isofunctional, catalyzing the conversion of 2-PGA to phosphoenolpyruvate. In the MLE subclass of the superfamily, at least three reactions are known to be catalysed — in addition to the lactonisation of muconate, succinylbenzoate synthase, and L-Ala-D/L-Glu epimerase reactions are observed within the 300 members. The MR subclass catalyses at least five reactions, mandelate racemisation and 4 sugar dehydratases. As in the MLE subclass, of the 400 members identified, only 50% of these are functionally assigned. 

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