| Abstract
| - We have discovered a superfamily of enzymes related bytheir ability to catalyze the abstractionof the α-proton of a carboxylic acid to form an enolic intermediate.Although each reaction catalyzed bythese enzymes is initiated by this common step, their overall reactions(including racemization, β-eliminationof water, β-elimination of ammonia, and cycloisomerization) as wellas the stereochemical consequences(syn vs anti) of the β-elimination reactions are diverse.Analysis of sequence and structural similaritiesamong these proteins suggests that all of their chemical reactions aremediated by a common active sitearchitecture modified through evolution to allow the enolicintermediates to partition to different productsin their respective active sites via different overallmechanisms. All of these enzymes retain the abilityto catalyze the thermodynamically difficult step of proton abstraction.These homologous proteins,designated the “enolase superfamily”, include enolase as well asmore metabolically specializedenzymes: mandelate racemase, galactonate dehydratase, glucaratedehydratase, muconate-lactonizingenzymes, N-acylamino acid racemase, β-methylaspartateammonia-lyase, and o-succinylbenzoate synthase.Comparative analysis of structure−function relationships withinthe superfamily suggests that carboxyphosphonoenolpyruvate synthase, another member of the superfamily, doesnot catalyze the reactionproposed in the literature but catalyzes an enolase-like reactioninstead. The established and deducedstructure−function relationships in the superfamily allow theprediction that other apparent members ofthe family for which no catalytic functions have yet been assigned willalso perform chemistry involvingabstraction of the α-protons of carboxylic acids.
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