Discrimination between the binding sites of modulators of the H+-translocating ATPase activity in rat liver mitochondrial membranes

Partis, Michael D.; Griffiths, David G.; Beechey, R. B.

doi:10.1016/0003-9861(84)90580-0

Cited by 6 publications

(7 citation statements)

References 26 publications

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“…From earlier experiments, subunit c was regarded as the primary target for organotins (6,30). However, these experiments were unable to exploit the use of a covalent proteininhibitor complex as reported here.…”

Section: Photoaffinity Labeling Of Atp Synthase and C-oligomer With Dmentioning

confidence: 88%

The ion channel of F-ATP synthase is the target of toxic organotin compounds

Ballmoos

Brunner

Dimroth

2004

Proc. Natl. Acad. Sci. U.S.A.

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ATP is the universal energy currency of living cells, and the majority of it is synthesized by the F 1 F 0 ATP synthase. Inhibitors of this enzyme are therefore potentially detrimental for all life forms. Tributyltin chloride (TBT-Cl) inhibits ATP hydrolysis by the Na ؉ -translocating ATP synthase of Ilyobacter tartaricus or the H ؉ -translocating counterpart of Escherichia coli with apparent K i of 200 nM. To target the site of this inhibition, we synthesized a tritium-labeled derivative of TBT-Cl in which one of the butyl groups was replaced by a photoactivatable aryldiazirine residue. Upon illumination, subunit a of the ATP synthase becomes specifically modified, and this labeling is suppressed in the presence of the original inhibitor. In case of the Na ؉ ATP synthase, labeling is also suppressed in the presence of Na ؉ ions, suggesting an interference in Na ؉ or TBT-Cl binding to subunit a. This interference is corroborated by the protection of ATP hydrolysis from TBT-Cl inhibition by 105 mM Na ؉ . TBT-Cl strongly inhibits Na ؉ exchange by the reconstituted I. tartaricus ATP synthase. Taken together these results indicate that the subunit a ion channel is the target site for ATPase inhibition by toxic organotin compounds. An inhibitor interacting specifically with this site has not been reported previously.

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Section: Photoaffinity Labeling Of Atp Synthase and C-oligomer With Dmentioning

confidence: 88%

The ion channel of F-ATP synthase is the target of toxic organotin compounds

Ballmoos

Brunner

Dimroth

2004

Proc. Natl. Acad. Sci. U.S.A.

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“…Azido derivatives of uncouplers have been synthesized in an attempt to identify an uncoupler binding protein (234)(235)(236)(237)(238)(239)(240)(241). A typical example is that of 2-azido-4-nitrophenyl, a structural analog of the classical uncoupler 2,4dinitrophenol (234).…”

Section: Photoaffinity Labelsmentioning

confidence: 99%

Chemical Probes of the Mitochondrial Atp Synthesis and Translocation

Vignais¹,

Lunardi²

1985

Annu. Rev. Biochem.

103

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“…Interestingly, both P. denitrificans and E. coli contain protein that is immunologically cross-reactive with FB (48,96). Uncouplerand inhibitor-binding sites have also been found in rat liver submitochondrial particles labeled with N3CCP, DCCD, or the trialkyl tin compound dibutylchloromethyl tin (80). In each case, radioactivity was concentrated in a single band of 10 to 16 kDa, but further electrophoretic and chromatographic separation indicated that three different proteins were involved.…”

Section: Related Observations and Phenomenamentioning

confidence: 96%

Uncoupler-resistant mutants of bacteria.

Krulwich

Quirk

Guffanti

1990

Microbiological Reviews

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be shown to have unaltered susceptibility to the effect of the uncouplers upon the AjjH'+, are of considerable bioenergetic interest. At least at first blush, their retention of bioenergetic work capacity at submaximal values of the AILH+ appears to represent a departure from the chemiosmotic formulation. In that formulation, the steady-state level of bioenergetic work, represented by, for example, the phosphorylation potential, AG,, is in direct and complete equilibrium with the AlUH+, and the AGpl/AiH+ ratio simply reflects the number of H+ ions translocated per ATP molecule synthesized (17, 25, 26, 55). It is not trivial to rigorously demonstrate that a resistant mutant strain is still fully sensitive to the effect of the agent on the AgIH±. Even in simple artificial systems, protono

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Discrimination between the binding sites of modulators of the H+-translocating ATPase activity in rat liver mitochondrial membranes

Cited by 6 publications

References 26 publications

The ion channel of F-ATP synthase is the target of toxic organotin compounds

The ion channel of F-ATP synthase is the target of toxic organotin compounds

Chemical Probes of the Mitochondrial Atp Synthesis and Translocation

Uncoupler-resistant mutants of bacteria.

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