Cation hexaammines are selective and potent inhibitors of the CorA magnesium transport system
Cation hexaammines are selective and potent inhibitors of the CorA magnesium transport system
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DOI：
10.1074/jbc.m001507200
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发表时间：
2000-06-02
影响因子：
4.8
通讯作者：
Maguire, ME
中科院分区：
文献类型：
--
作者：
Kucharski, LM;Lubbe, WJ;Maguire, ME
阳离子六胺和相关化合物是阳离子水合形式的化学稳定类似物，特别是Mg 2+：我们测试了这些化合物中的几种抑制鼠伤寒沙门氏菌中CorA或MgtB Mg 2+转运系统或PhoQ受体激酶转运Mg 2+的能力。钴（III）-、钌（II）-和钌（III）-六胺是CorA介导的内流的有效抑制剂，钴（III）-和钌（III）氯五胺是CorA的略弱的有效抑制剂。这些化合物抑制细菌S. typhimurium CorA和古细菌詹氏甲烷球菌CorA，它们在细胞外周质结构域中仅具有12%的同一性。阳离子六胺也能抑制S.依赖于CorA的鼠伤寒沙门氏菌菌株对Mg ~（2+）的摄取，但不依赖于携带第二Mg ~（2+）摄取系统的等基因菌株。相比之下，六氰基钴（III）和六烯酸（II）-和镍（II）六胺对摄取的影响很小。阳离子六胺的抑制对CorA具有选择性，因为这些化合物对MgtB P型ATP酶Mg 2+转运蛋白或PhoQ Mg 2+受体激酶的转运没有任何影响。这些结果表明，阳离子六胺是CorA Mg 2+转运系统的有效和高选择性抑制剂，并进一步表明CorA转运蛋白的初始相互作用是与完全水合的Mg 2+阳离子。
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.