Sodium and Potassium Ions in Proteins and Enzyme Catalysis

Abstract

The group I alkali metal ions Na⁺ and K⁺ are ubiquitous components of biological fluids that surround biological macromolecules. They play important roles other than being nonspecific ionic buffering agents or mediators of solute exchange and transport. Molecular evolution and regulated high intracellular and extracellular M⁺ concentrations led to incorporation of selective Na⁺ and K⁺ binding sites into enzymes to stabilize catalytic intermediates or to provide optimal positioning of substrates. The mechanism of M⁺ activation, as derived from kinetic studies along with structural analysis, has led to the classification of cofactor-like (type I) or allosteric effector (type II) activated enzymes. In the type I mechanism substrate anchoring to the enzyme active site is mediated by M⁺, often acting in tandem with a divalent cation like Mg²⁺, Mn²⁺ or Zn²⁺. In the allosteric type II mechanism, M⁺ binding enhances enzyme activity through conformational transitions triggered upon binding to a distant site. In this chapter, following the discussion of the coordination chemistry of Na⁺ and K⁺ ions and the structural features responsible for the metal binding site selectivity in M⁺-activated enzymes, well-defined examples of M⁺-activated enzymes are used to illustrate the structural basis for type I and type II activation by Na⁺ and K⁺.

Please cite as: Met. Ions Life Sci. 16 (2016) 259–290