The group I monovalent cations Na + and K + and ammonium ion are important effectors of catalytic activity for a wide variety of enzymes. Until recently, little was known about the mechanism of action of these effectors. However, in the past year, X-ray structures of three metal-ion-activated pyridoxal phosphate (PLP)-requiring enzymes have been solved. This information together with solution studies of these and related enzymes have provided new insights into the relationship between structure and function for monovalent cation-activated enzymes. By drawing on the extensive literature concerning the complexes formed between macrocyclic multidentate chelators and group I metal ions, this review examines the relationships between the properties of the metal ions, chelator affinity and binding specificity. This information is integrated with the structural information on the metal ion sites of monovalentmetal-ion-activated PLP enzymes and mechanistic hypotheses for the metal-ion-mediated interconversion of inactive and active forms of this class of enzymes. The available X-ray structures show in each case the active site(s) and the metal ion binding site(s) at distinctly separate loci. Consequently, in these systems the metal ion cofactor is properly classified as an allosteric effector that does not participate directly in bonding interactions with the reacting substrate. It is concluded that, under most physiological conditions, these effector sites are saturated, and binding of the metal ion is a permanent feature of catalysis. Given these constraints, two types of mechanism are considered to explain the effects of monovalent metal ions on catalytic activity: (1) mechanisms involving the metal ion in a static structural role wherein binding activates the enzyme by simply stabilizing the catalytically active conformation of the protein and (2) mechanisms where the metal ion plays a dynamic role in which binding selectively assists one or more of the protein conformational transitions essential for complementarity between enzyme site and the structure of an activated complex.