Effects of the Inhibitors Azide, Dicyclohexylcarbodiimide, and Aurovertin on Nucleotide Binding to the Three F1-ATPase Catalytic Sites Measured Using Specific Tryptophan Probes

Weber, Joachim; Senior, Alan E.

doi:10.1074/jbc.273.50.33210

Cited by 44 publications

(47 citation statements)

References 31 publications

(30 reference statements)

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“…Thiocyanate and cyanate have similar inhibitory effects on the F 1 -ATPase to azide (32), and because of the similarities of their shapes and charge distributions to azide (32), it is likely that their inhibitory mechanisms are also similar. There was no evidence for bound azide elsewhere in the electron density map, including the regions corresponding to the ␣-subunits, so the structure does not support the proposition that azide blocks cooperation between catalytic sites (26,27).…”

Section: ͚H͚i͉i(h) ϫ I(h)i͉͚͞h͚ii(h)i Where I(h)mentioning

confidence: 66%

“…It has been proposed that this inhibitory effect of ADP⅐Mg 2ϩ is enhanced by azide (5,6,22,24). Another explanation that has been advanced to explain the inhibitory effect of azide is that it blocks cooperation between catalytic sites (26,27). Rotation of the ␥-subunit in the synthetic direction in an F 1 -ATPase complex inhibited with ADP and azide expels them from the enzyme (28), and ADP and azide do not inhibit ATP synthesis (4).…”

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confidence: 99%

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How azide inhibits ATP hydrolysis by the F-ATPases

Bowler

Montgomery

Leslie

et al. 2006

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

227

180

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In the structure of bovine F1-ATPase determined at 1.95-Å resolution with crystals grown in the presence of ADP, 5 -adenylylimidodiphosphate, and azide, the azide anion interacts with the ␤-phosphate of ADP and with residues in the ADP-binding catalytic subunit, ␤DP. It occupies a position between the catalytically essential amino acids, ␤-Lys-162 in the P loop and the ''arginine finger'' residue, ␣-Arg-373, similar to the site occupied by the ␥-phosphate in the ATP-binding subunit, ␤TP. Its presence in the ␤DP-subunit tightens the binding of the side chains to the nucleotide, enhancing its affinity and thereby stabilizing the state with bound ADP. This mechanism of inhibition appears to be common to many other ATPases, including ABC transporters, SecA, and DNA topoisomerase II␣. It also explains the stimulatory effect of azide on ATP-sensitive potassium channels by enhancing the binding of ADP.mitochondria ͉ oxidative phosphorylation ͉ inhibition ͉ mechanism

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Section: ͚H͚i͉i(h) ϫ I(h)i͉͚͞h͚ii(h)i Where I(h)mentioning

confidence: 66%

mentioning

confidence: 99%

How azide inhibits ATP hydrolysis by the F-ATPases

Bowler

Montgomery

Leslie

et al. 2006

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

227

180

View full text Add to dashboard Cite

show abstract

“…In bacteria that are naturally resistant to aurovertin, the ␤-Arg398 residue is replaced with other amino acid residues (172, 343). Aurovertin is believed to inhibit F 1 by preventing catalytic interface closure involved in the cyclic interconversion of catalytic sites (410,430). In addition, aurovertin increases the affinity of F 1 for phosphate (307).…”

Section: Polyenic ␣-Pyrone Derivativesmentioning

confidence: 99%

ATP Synthase and the Actions of Inhibitors Utilized To Study Its Roles in Human Health, Disease, and Other Scientific Areas

Hong

Pedersen

2008

Microbiol Mol Biol Rev

275

302

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SUMMARY ATP synthase, a double-motor enzyme, plays various roles in the cell, participating not only in ATP synthesis but in ATP hydrolysis-dependent processes and in the regulation of a proton gradient across some membrane-dependent systems. Recent studies of ATP synthase as a potential molecular target for the treatment of some human diseases have displayed promising results, and this enzyme is now emerging as an attractive molecular target for the development of new therapies for a variety of diseases. Significantly, ATP synthase, because of its complex structure, is inhibited by a number of different inhibitors and provides diverse possibilities in the development of new ATP synthase-directed agents. In this review, we classify over 250 natural and synthetic inhibitors of ATP synthase reported to date and present their inhibitory sites and their known or proposed modes of action. The rich source of ATP synthase inhibitors and their known or purported sites of action presented in this review should provide valuable insights into their applications as potential scaffolds for new therapeutics for human and animal diseases as well as for the discovery of new pesticides and herbicides to help protect the world's food supply. Finally, as ATP synthase is now known to consist of two unique nanomotors involved in making ATP from ADP and Pi, the information provided in this review may greatly assist those investigators entering the emerging field of nanotechnology.

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“…It has been proposed that this is due to the binding of inhibitory MgADP to a catalytic site on the enzyme [32][33][34][35][36][37]. However, Harris [38] and Weber and Senior [39] have suggested that azide inhibits ATP hydrolysis of F " by abolishing the intersubunit co-operativity of the catalytic sites. Moreover, Weber and Senior [39] did not find bound MgADP during hydrolysis of ATP under turnover conditions in the presence of azide.…”

Section: Discussionmentioning

confidence: 99%

“…However, Harris [38] and Weber and Senior [39] have suggested that azide inhibits ATP hydrolysis of F " by abolishing the intersubunit co-operativity of the catalytic sites. Moreover, Weber and Senior [39] did not find bound MgADP during hydrolysis of ATP under turnover conditions in the presence of azide. Little information is available on the effect of azide on F " F o -ATP synthase.…”

Section: Discussionmentioning

confidence: 99%