Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 101, Issue 31, Pages 11239-11244Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0402869101
Keywords
-
Categories
Ask authors/readers for more resources
ATP is the universal energy currency of living cells, and the majority of it is synthesized by the F1F0 ATIP synthase. Inhibitors of this enzyme are therefore potentially detrimental for all life forms. Tributyltin chloride (TBT-CI) 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 TIBT-CI in which one of the butyl groups was replaced by a photoactivatable aryidiazirine residue. Upon illumination, subunit a of the ATIP synthase becomes specifically modified, and this labeling is suppressed in the presence of the original inhibitor. In case of the Na+ ATIP synthase, labeling is also suppressed in the presence of Na+ ions, suggesting an interference in Na+ or TBT-CI binding to subunit a. This interference is corroborated by the protection of ATP hydrolysis from TIBT-CI inhibition by 105 mM Na+. TBT-CI strongly inhibits Na+ exchange by the reconstituted L 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available