The enolase superfamily: Different reactions catalyzed by similar active sites

The members of the enolase superfarnily of enzymes are related by their ability to catalyze abstraction of an a-proton from a carboxylic acid substrate to generate stabilized enolate/enolic intermediates. These intermediates partition to the diverse products by different mechanisms, including racemization/epirnerization, -elimination of water or ammonia, and cycloisomerizatiort. I.ike all members of their fold class, the rf/tt barrels, the active sites are located in a depression defined by the ('-terminal ends of the eight 3she<'ts: the functional groups involved in catalysis are located at the ends of separate J sheets. This location of functional groups allows chemistry to be (re (directed from a variety of geometric orientations relative to the bound substrates, thereby allowing the evolution of new catalytic functions while retaining the ability to generate enolate/enoHc intermediates. Details of the dependence of function on structure are being characterized in several members of the enolase superfamily, including mandelate racemase. galattnnate and glucarate dehydraiases, N-acylamtnoacid racemase, and carboxyphosphonoenolpynivate synithase.