Isotope effects in the study of enzymatic phosphoryl transfer reactions

Protein-tyrosine phosphatases and serine/threonine protein phosphatases uti lize very different catalytic machinery to catalyze phosphoryl transfer rea ctions. Tyrosine is a better leaving group than serine or threonine, having a pK(a) more than three units lower. Has the difference in the catalytic m achinery used by these enzyme families evolved as a result of the differenc e in the]ability of their substrates? Are the transition states for phospho ryl transfer similar for the two classes of enzymes? This review summarizes what has been learned from kinetic isotope effects about the nature of enz ymatic phosphoryl transfer, and how the enzymatic mechanisms compare to unc atalyzed phosphoryl transfer reactions. (C) 2001 Published by Elsevier Scie nce B.V. on behalf of the Federation of European Biochemical Societies.