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

Abstract

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+ uptake 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.