Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.3.14 (ATP synthase)
 7,042 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:The ion channel of F-ATP synthase is the target of toxic organotin compounds. 1527 81

A proteomic study of Cunninghamella echinulata recovery during exposure to tributyltin was conducted with 2-D SDS-PAGE protein separation and profiling, MALDI-TOF/TOF protein identification, and PCA analysis. The presence of TBT resulted in an upregulation of enzymes related to energy production via cellular respiration. The unique overexpression of NADH dehydrogenase and mitochondrial malate dehydrogenase, together with an increased level of cytochrome c oxidase, ATP synthase subunits, and inorganic pyrophosphatase, indicates a strong energy deficit in the cells, leading to an increase in the ATP production. The overexpression of Prohibitin-1, a multifunctional protein associated with the proper functioning of mitochondria, was observed as well. The data also revealed oxidative stress condition. Among reactive oxygen species (ROS)-scavenging enzymes, only superoxide dismutase (SOD) showed active response against oxidative stress induced by the xenobiotic. The induction of a series of ROS-scavenging enzymes was supported by a microscopic analysis revealing a considerably large concentration of ROS in the hyphae. The overexpression of cytoskeleton-related proteins in the TBT presence was also noticed. The obtained results allow explaining the recovery strategy of the fungus in response to the energy depletion caused by TBT.
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PMID:A proteomic study of Cunninghamella echinulata recovery during exposure to tributyltin. 3162 17