Key Features Of Magnesium That Underpin Its Role As The Major Ion For Electrophilic Biocatalysis

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 (HCO3-). 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.