The effects of exchange-inert metal—Nucleotide complexes on the kinetics of beef heart mitochondrial F1-ATPase

Steinke, Laurey; Bacon, Raymond F.; Schuster, Sheldon M.

doi:10.1016/0003-9861(87)90369-9

Cited by 4 publications

(5 citation statements)

References 33 publications

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“…The exchange-inert metal-nucleotide complexes inhibit ATP synthase by binding to F 1 (44,158,383,384,432). Chromium complexes of ATP and ADP, i.e., ␣,␤-CrADP, ␤,␥-CrATP, and ␣,␤,␥-CrATP, are competitive inhibitors of MF 1 with respect to MgATP (383, 432).…”

Section: Purine Nucleotides and Nucleotide Analogsmentioning

confidence: 99%

“…␤,␥-CrATP and ␣,␤,␥-CrATP bind to the catalytic site with the same affinity, although they have different steric arrangements of the chromium (␤,␥-CrATP with monocyclic coordination at the metal ion and ␣,␤,␥-CrATP with bicyclic coordination). Two diastereomers of ␣,␤-CrADP (⌳ and ⌬ isomers) also exert similar inhibitory effects (432 (44,158,383,384). All the amine and aqua exchange-inert metalnucleotide complexes are mutually exclusive during ATP hydrolysis and appear to bind the same site(s) (383).…”

Section: Purine Nucleotides and Nucleotide Analogsmentioning

confidence: 99%

“…Two diastereomers of ␣,␤-CrADP (⌳ and ⌬ isomers) also exert similar inhibitory effects (432 (44,158,383,384). All the amine and aqua exchange-inert metalnucleotide complexes are mutually exclusive during ATP hydrolysis and appear to bind the same site(s) (383).…”

Section: Purine Nucleotides and Nucleotide Analogsmentioning

confidence: 99%

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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

276

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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Section: Purine Nucleotides and Nucleotide Analogsmentioning

confidence: 99%

Section: Purine Nucleotides and Nucleotide Analogsmentioning

confidence: 99%

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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

276

302

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“…Previous studies reported that β,γ-Cr(III)ATP and α,β,γ-Cr(III)ATP inhibited F 1 -ATPase by binding at the catalytic site with the same affinity and α,β-Cr(III)ATP by binding at a regulatory site, and the binding sites showed no significant selectivity for the steric arrangement of the Cr(III) complexes 58 , 59 . Our findings are reconciling with previous reports that Cr 3+ -ADP/ATP could competitively inhibit mitochondrial F 1 -ATPase employing Mg 2+ -ADP/ATP as a substrate 45 , 58 – 60 . It is worth mentioning that other transition metal ions such as Zn 2+ and Mn 2+ could inhibit ATP synthase in vitro 59 , 61 , however, the bindings of these transition metal ions (including Zn 2+ , Mn 2+ , Cu 2+ , Co 2+ , Ni 2+ , and Fe 3+ ) are not as strong as Cr 3+ as evidenced by the binding affinities and competition studies (Supplementary Fig.…”

Section: Discussionmentioning

confidence: 92%

“…Nevertheless, we provide direct evidence that Cr 3+ inhibits ATP synthase via displacement of Mg 2+ from ATP5B. Previous studies reported that β,γ-Cr(III)ATP and α,β,γ-Cr(III)ATP inhibited F 1 -ATPase by binding at the catalytic site with the same affinity and α,β-Cr(III)ATP by binding at a regulatory site, and the binding sites showed no significant selectivity for the steric arrangement of the Cr(III) complexes 58 , 59 . Our findings are reconciling with previous reports that Cr 3+ -ADP/ATP could competitively inhibit mitochondrial F 1 -ATPase employing Mg 2+ -ADP/ATP as a substrate 45 , 58 – 60 .…”

Section: Discussionmentioning

confidence: 95%

Mitochondrial ATP synthase as a direct molecular target of chromium(III) to ameliorate hyperglycaemia stress

Wang

et al. 2023

Nat Commun

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Chromium(III) is extensively used as a supplement for muscle development and the treatment of diabetes mellitus. However, its mode of action, essentiality, and physiological/pharmacological effects have been a subject of scientific debate for over half a century owing to the failure in identifying the molecular targets of Cr(III). Herein, by integrating fluorescence imaging with a proteomic approach, we visualized the Cr(III) proteome being mainly localized in the mitochondria, and subsequently identified and validated eight Cr(III)-binding proteins, which are predominately associated with ATP synthesis. We show that Cr(III) binds to ATP synthase at its beta subunit via the catalytic residues of Thr213/Glu242 and the nucleotide in the active site. Such a binding suppresses ATP synthase activity, leading to the activation of AMPK, improving glucose metabolism, and rescuing mitochondria from hyperglycaemia-induced fragmentation. The mode of action of Cr(III) in cells also holds true in type II diabetic male mice. Through this study, we resolve the long-standing question of how Cr(III) ameliorates hyperglycaemia stress at the molecular level, opening a new horizon for further exploration of the pharmacological effects of Cr(III).

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A vector method of representation of enzymic reactions

Krupyanko

2004

Process Biochemistry

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The effects of exchange-inert metal—Nucleotide complexes on the kinetics of beef heart mitochondrial F1-ATPase

Cited by 4 publications

References 33 publications

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

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

Mitochondrial ATP synthase as a direct molecular target of chromium(III) to ameliorate hyperglycaemia stress

A vector method of representation of enzymic reactions

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