Role of Na⁺and K⁺in Enzyme Function

Abstract

Metal complexation is a key mediator or modifier of enzyme structure and function. In addition to divalent and polyvalent metals, group IA metals Na+ and K+ play important and specific roles that assist function of biological macromolecules. We examine the diversity of monovalent cation (M+)-activated enzymes by first comparing coordination in small molecules followed by a discussion of theoretical and practical aspects. Select examples of enzymes that utilize M+ as a cofactor (type I) or allosteric effector (type II) illustrate the structural basis of activation by Na+ and K+, along with unexpected connections with ion transporters. Kinetic expressions are derived for the analysis of type I and type II activation. In conclusion, we address evolutionary implications of Na+ binding in the trypsin-like proteases of vertebrate blood coagulation. From this analysis, M+ complexation has the potential to be an efficient regulator of enzyme catalysis and stability and offers novel strategies for protein engineering to improve enzyme function.

Characterization of protease activities in a crude extract of germinated cacao

“…The effect of the ionic strength of sodium chloride revealed that activity increases when the former increases in the medium. Monovalent cation coordination plays an influential role in many enzyme-catalysed reactions (Di Cera, 2006;Page & Di Cera, 2006). Due to limited electrostatic properties, Na + and K + are optimal reagents for stabilization of the active conformational state of an enzyme or for facilitating electrostatic interactions between enzyme and substrate (Page & Di Cera, 2008).…”

The integration of activity in saline environments: problems and perspectives

“…Some of the dependencies are for specific ions, especially cations (e.g. K + , Na + or Mg 2+ ) and some are general (Suelter 1970;Clarkson and Hanson 1980;Nayal and DiCera 1996;Page and Di Cera 2006). Some of these dependencies that are evident in vitro disappear in vivo, possibly reflecting the consequences of condensation of enzymes into large complexes, i.e.…”

Is it possible to transform trypsin to thrombin?

“…These sites coordinate interactions with substrates, inhibitors, cofactors, and effector molecules. Coagulation proteases also belong to the large family of Na þ -activated enzymes (8,9). Na þ binds at a different site below the primary specificity pocket (S1) of the enzyme and is coordinated by residues neither directly involved in catalysis nor substrate recognition.…”