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Journal article

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

  • 2004-07-28
Published in:
  • Proceedings of the National Academy of Sciences of the United States of America. - 2004
Adenosine Triphosphatases
Adenosine Triphosphate
Binding Sites
Cation Transport Proteins
Cell Membrane
Enzyme Inhibitors
Escherichia coli
Mitochondrial Proton-Translocating ATPases
Organotin Compounds
Photoaffinity Labels
Photochemistry
Proteolipids
Sodium
Solubility
Trialkyltin Compounds
English ATP is the universal energy currency of living cells, and the majority of it is synthesized by the F1F0 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 Ki 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.
Language
  • English
Open access status
bronze
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Persistent URL
https://folia.unifr.ch/global/documents/52629
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