MAGNESIUM ACTIVATION OF NUCLEASE ENZYMES - THE IMPORTANCE OF WATER

Enzymatic metal-mediated hydrolysis of phosphate esters may proceed th rough either inner- or outer-sphere pathways. Theoretical and experime ntal consideration of this problem suggests that outer-sphere pathways should predominate for magnesium-promoted reactions, where hydrogen b onding to metal-bound waters is the dominant stabilizing interaction. Comparison of a variety of magnesium-dependent enzymes reflects a requ irement for differentially hydrated metal cofactor, which can only be achieved by limiting the number of protein ligands to the metal. As a result, these enzymes have evolved distinct mechanisms for control of metal binding affinities (K-D), all of which lie in the range of simil ar to 0.5 mM. This article describes and discusses these issues, which have not previously been considered in detail. (C) 1998 Elsevier Scie nce S.A. All rights reserved.