Abstract
The simplest chemical transformations in metabolism are the proton transfer reactions exemplified by certain isomerases and racemases. We have been studying three such enzymes to understand the structural features that lead to efficient proton transfer. All of these enzymes face the common problem of abstracting a hydrogen from a carbon acid of high pKa with an enzymic base of low pKa. We have used X-ray crystallography, site-directed mutagenesis, and molecular dynamics simulations to arrive at a set of principles for optimal catalysis of this simple reaction.