Key features of magnesium that underpin its role as the major ion for electrophilic biocatalysis

Abstract

To investigate divalent metal ion (Me²⁺ ) requirements in electrophilic biocatalysis, we compared Mg²⁺ , Mn²⁺ , Co²⁺ , Zn²⁺ , Cu²⁺ , Ni²⁺ , Cd²⁺ , Ca²⁺ , and Fe²⁺ activities with 13 enzymes executing nucleotidyl and/or phosphoryl transfer. We find that each Me²⁺ ion was highly catalytically active with one or more of the related enzymes. This result suggests that features of Me²⁺ coordination at the active center, and/or the enzyme-mediated presentation of the reactants to the chelated Me²⁺ , rather than the nature of the Me²⁺ , determine the ability of the Me²⁺ to support catalysis. At physiological pH, all the tested Me²⁺ ions, with the exception of Mg²⁺ , produced insoluble complexes with inorganic phosphate (P_i ) and bicarbonate ( ${\text{HCO}}_3^{-}$ ). These data suggest that early in the development of life, bioavailability and biocompatibility with these abundant cellular metabolites may have been decisive factors in the choice of Mg²⁺ as the major ion for biocatalysis. Taking into account the concentrations of inorganic ions in the ancient environment in which the first cells emerged, as inferred from the 'chemistry conservation principle', the choice of Mg²⁺ was predetermined prior to the origin of life.

Keywords: carbonate; catalysis; divalent metal ions; nucleic acid enzymes; phosphate.