Epimerases: structure, function and mechanism

Carbohydrates are ideally suited for molecular recognition. By varying the stereochemistry of the hydroxyl substituents, the simple six-carbon, six-ox ygen pyranose ring can exist as 10 different molecules. With the further ad dition of simple chemical changes, the potential for generating distinct mo lecular recognition surfaces far exceeds that of amino acids. This ability to control and change the stereochemistry of the hydroxyl substituents is v ery important in biology. Epimerases can be found in animals, plants and mi croorganisms where they participate in important metabolic pathways such as the Leloir pathway, which involves the conversion of galactose to glucose- 1-phosphate. Bacterial epimerases are involved in the production of complex carbohydrate polymers that are used in their cell walls and envelopes and are recognised as potential therapeutic targets for the treatment of bacter ial infection. Several distinct strategies have evolved to invert or epimer ise the hydroxyl substituents on carbohydrates. In this review we group epi merisation by mechanism and discuss in detail the molecular basis for each group. These groups include enzymes which epimerise by a transient keto int ermediate, those that rely on a permanent keto group, those that eliminate then add a nucleotide, those that break then reform carbon-carbon bonds and those that linearize and cyclize the pyranose ring. This approach highligh ts the quite different biochemical processes that underlie what is seemingl y a simple reaction. What this review shows is that each position on the ca rbohydrate can be epimerised and that epimerisation is found in all organis ms.