Cation hexaammines are selective and potent inhibitors of the CorA magnesium transport system

Cation hexaammines and related compounds are chemically stable analogs of the hydrated form of cations, particularly Mg2+: We tested the ability of several of these compounds to inhibit transport by the CorA or MgtB Mg2+ transport systems or the PhoQ receptor kinase for Mg2+ in Salmonella typhimurium. Cobalt(III)-, ruthenium(II)-, and ruthenium(III)-hexaammines were potent inhibitors of CorA-mediated influx, Cobalt(III)-and ruthenium(III)chloropentaammines were slightly less potent inhibitors of CorA. The compounds inhibited uptake by the bacterial S. typhimurium CorA and by the archaeal Methanococcus jannaschii CorA, which bear only 12% identity in the extracellular periplasmic domain. Cation hexaammines also inhibited growth of S. typhimurium strains dependent on CorA for Mg2+ up- take but not of isogenic strains carrying a second Mg2+ uptake system. In contrast, hexacyano-cobaltate (III) and ruthenate(II)- and nickel(II)hexaammine had little effect on uptake, The inhibition by the cation hexaammines was selective for CorA because none of the compounds had any effect on transport by the MgtB P-type ATPase Mg2+ transporter or the PhoQ Mg2+ receptor kinase. These results demonstrate that cation hexaammines are potent and highly selective inhibitors of the CorA Mg2+ transport system and further indicate that the initial interaction of the CorA transporter is with a fully hydrated Mg2+ cation.