Active/inactive state transitions of mitochondrial ATPase molecules influenced by Mg<sup>2+</sup>, anions and aurovertin

Moyle, Jennifer; Mitchell, Peter

doi:10.1016/0014-5793(75)80110-4

Cited by 115 publications

(64 citation statements)

References 19 publications

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“…The onset of the inhibition is rather slow (seconds to minutes). The Mg 2ϩ ADP-induced inhibition can be slowly and partially reversed by addition of ATP in the absence of Mg 2ϩ (272), and the recovery of ATPase activity requires the binding of ATP at a noncatalytic site. The recovery is promoted by anions such as bicarbonate and sulfite (272,412).…”

Section: Purine Nucleotides and Nucleotide Analogsmentioning

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

274

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%

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

274

302

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“…The F 1 -ATPase as conventionally isolated usually has a considerable portion with tight ADP present. In 1975, Moyle and Mitchell reported that mitochondrial F 1 -ATPase was slowly inactivated by Mg 2ϩ (83). Hackney noted the inhibition was slowly reversible by ATP addition (84).…”

Section: The Insidious Mgadp Inhibitionmentioning

confidence: 99%

A Research Journey with ATP Synthase

Boyer¹

2002

Journal of Biological Chemistry

117

102

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These reflections present a perspective of how I and my graduate students and postdoctoral fellows, over a span of many years, arrived at the concept that ATP is made by an unusual rotational catalysis of the ATP synthase. A recent sketch of the structure of this remarkable enzyme is given in Fig. 1. Such a depiction is the culmination of the efforts of many investigators.1 The two portions of the enzyme are the membrane-imbedded F 0 and the attached F 1 that has three catalytic sites, principally on the large ␤ subunits. ATP is formed when protons pass through the F 0 , driving the rotation of the ring-shaped cluster of c subunits and the attached ⑀ and ␥ subunits. Other subunits attached to outer portions of the F 0 and F 1 served as a stator. The internal rotary movement of the ␥ subunit is coupled to sequential changes in the conformation of the catalytic sites. During ATP synthesis these conformational changes promote the binding of ADP and P i , the formation of tightly bound ATP, and the release of ATP.Revealing the mechanism of the ATP synthase became a major research goal in the latter part of my long career. This paper recalls how my career developed as related to the remarkable progress in biochemical knowledge. It presents the background and results of fruitful, as well as mistaken, approaches that were explored. The Early YearsBorn and educated through college in Utah, at the age of 21 I entered graduate school in the Department of Biochemistry at the University of Wisconsin in the fall of 1939. The biochemical research and teaching there were excellent. Not until years later did I appreciate all that is necessary to create such a fine scientific environment.I had had no previous courses or research experience in biochemistry and was uncertain about my career choice. By the end of my first year of graduate study the fascination of biochemical understanding and the addictive effect of experimental attempts to uncover new knowledge had firmly launched me toward a career in biochemical research. The Department of Biochemistry at Wisconsin was at the forefront of research in nutrition and metabolism. Recent achievements included the identification of nicotinic acid as a vitamin, the irradiation of milk to produce vitamin D, the discovery of a vitamin K antagonist (dicoumarin), and the discovery of lipoic acid as a growth factor for bacteria. At that time incoming graduate students were assigned to a mentor professor. Both Henry Lardy, from South Dakota, and I joined the group of Professor Paul Phillips whose major interest was in dairy cattle nutrition. Evidence had been obtained that vitamin C might help prevent reproductive difficulties in cattle, and one of my assignments was to find if vitamin C might ameliorate the reproductive failure that occurred in rats with vitamin E deficiency. No benefits of vitamin C were noted, but the rats 1 Except for a few instances, the mention of important advances in information about the ATP synthase and in related areas of biochemistry is included without specific ...

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“…It is possible that heating provokes a transition of part of F, from an inactive form into an active form. Moyle and Mitchell [24] suggested for F1 from beef heart or rat liver, the existence of both an inactive and active form. The number of accessible thiol groups of the active form would be lower than those of the active form; the slow recovery of the heated enzyme (Table 3) would be in agreement with Moyle and Mitchell hypothesis i.e.…”

Section: Thiol Reactivity Of Unheated and Heated Enzyme Ir? The Presementioning

confidence: 99%

Masking of co‐operativity of nucleotide sites in pig heart mitochondrial ATPase (F₁) by heating

1975

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Active/inactive state transitions of mitochondrial ATPase molecules influenced by Mg²⁺, anions and aurovertin

Cited by 115 publications

References 19 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

A Research Journey with ATP Synthase

Masking of co‐operativity of nucleotide sites in pig heart mitochondrial ATPase (F₁) by heating

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Active/inactive state transitions of mitochondrial ATPase molecules influenced by Mg2+, anions and aurovertin

Cited by 115 publications

References 19 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

A Research Journey with ATP Synthase

Masking of co‐operativity of nucleotide sites in pig heart mitochondrial ATPase (F1) by heating

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Product

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Active/inactive state transitions of mitochondrial ATPase molecules influenced by Mg²⁺, anions and aurovertin

Masking of co‐operativity of nucleotide sites in pig heart mitochondrial ATPase (F₁) by heating