Tentoxin An uncompetitive inhibitor of lettuce chloroplast coupling factor 1

Steele, John A.; Durbin, R. D.; Uchytil, Thomas F.; Rich, Daniel H.

doi:10.1016/0005-2728(78)90096-8

Cited by 52 publications

(25 citation statements)

References 14 publications

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“…At low concentrations, tentoxin acts as an uncompetitive inhibitor of the ATPase activity of CF 1 derived from certain sensitive plant species but not of homologous CF 1 s from chloroplasts of some other plant species. Also, tentoxin does not inhibit the ATPase activity of F 1 s derived from bacteria or mitochondria (19,378,380). Tentoxin also inhibits ATP synthesis in chloroplasts from the sensitive species.…”

Section: Tentoxin and Its Derivativesmentioning

confidence: 98%

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: Tentoxin and Its Derivativesmentioning

confidence: 98%

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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“…Tentoxin, a cyclic tetrapeptide (cyclo-L-leucyl-N-methyl-(z)-dehydrophenylalanyl-glycyl-N-methyl-alanyl) produced by the fungus Alternaria tenuis, is a potent inhibitor of the chloroplast ATP synthase of certain sensitive plant species (8,9), which acts as an uncompetitive inhibitor of the CF 1 -ATPase with respect to nucleotide substrates. It was proposed that 1 mol of tentoxin/mol of CF 1 , bound at a site near the interface between the N-terminal domains of subunits ␣ and ␤, interferes with the cooperative interaction between nucleotide binding sites inhibiting the enzyme activity (10).…”

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confidence: 99%

Catalytic Properties and Sensitivity to Tentoxin of Chlamydomonas reinhardtii ATP Synthases Changed in Codon 83 of atpB by Site-directed Mutagenesis

Fiedler

Golan

et al. 1997

Journal of Biological Chemistry

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The participation of the amino acid ␤83 in determining the sensitivity of chloroplast ATP synthases to tentoxin was reported previously. We have changed codon 83 of the Chlamydomonas reinhardtii atpB gene by sitedirected mutagenesis to further examine the role of this amino acid in the response of the ATP synthase to tentoxin and in the mechanism of ATP synthesis and hydrolysis. Amino acid ␤83 was changed from Glu to Asp (␤E83D) and to Lys (␤E83K), and the highly conserved tetrapeptide ␤T82-E83-G84-L85 (⌬TEGL) was deleted. Mutant strains were produced by particle gun transformation of atpB deletion mutants cw15⌬atpB and FUD50 with the mutated atpB genes. The transformants containing the ␤E83D and ␤E83K mutant genes grew well photoautotrophically. The ⌬TEGL transformant did not grow photoautotrophically, and no CF 1 subunits were detected by immunostaining of Western blots using CF 1 specific antibodies. The rates of ATP synthesis at clamped ⌬pH with thylakoids isolated from cw15 and the two mutants, ␤E83D and ␤E83K, were similar. However, only the phosphorylation activity of the mutant ␤E83D was inhibited by tentoxin with 50% inhibition attained at 4 M. These results confirm that amino acid ␤83 is critical in determining the response of ATP synthase to tentoxin. The rates of the latent Mg-ATPase activity of the CF 1 s isolated from cw15, ␤E83D, and ␤E83K were similar and could be enhanced by heat, alcohols, and octylglucoside. As in the case of the membrane-bound enzyme, only CF 1 from the ␤E83D mutant was sensitive to tentoxin. A lower alcohol concentration was required for optimal stimulation of the ATPase of the ␤E83K-CF 1 than that of CF 1 from the other two strains. Moreover, the optimal activity of the ␤E83K-CF 1 was also lower. These results suggest that introduction of an amino acid with a positively charged side chain in position 83 in the "crown" domain affects the active conformation of the CF 1 -ATPase.The eukaryotic unicellular green algae Chlamydomonas reinhardtii constitutes a powerful experimental model system for the study of the photosynthetic machinery. It is accessible to genetic analysis and grows photoautotrophically on minimal medium or heterotrophically with acetate as the sole carbon source. These properties have been used to isolate numerous photosynthetic mutants which have helped to examine the function of the photosynthetic apparatus (1).The chloroplast of C. reinhardtii contains approximately 80 copies of its 196-kb 1 circular genome (2). Due to recent progress in the molecular genetics of C. reinhardtii, chloroplast proteins can be altered by site-directed mutagenesis of the corresponding genes followed by transformation into the chloroplast (3-7). Chloroplast transformation was first demonstrated in 1988 by Boynton and co-workers (3), by complementation of an atpB deletion mutant with the cloned wild type gene. The transforming DNA integrates into the recipient chloroplast DNA by homologous recombination. Goldschmidt-Clermont (5) has constructed a chimeric selectable marker using ...

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“…At higher concentrations of tentoxin, binding of a second and possibly a third molecule to low-affinity sites (K D Ͼ 10 Ϫ6 ) has been observed (13,15). Surprisingly, binding of inhibitor molecules to these sites resulted in re-activation of ATP hydrolysis (12,13,15). The degree of both inhibition and re-activation of the enzyme varies; whereas spinach CF 1 showed about 80% maximal inhibition and reactivation to about 3-fold its activity in the absence of tentoxin, reduced sensitivity for inhibition and less pronounced re-activation were reported for chimeric complexes constructed from CF 1 and Rhodospirillum rubrum F 1 -ATPase subunits (16,17) and for CF 1 treated with synthetic tentoxin analogues (18).…”

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Complete Inhibition and Partial Re-activation of Single F1-ATPase Molecules by Tentoxin

Pavlova

Shimabukuro

Hisabori

et al. 2004

Journal of Biological Chemistry

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We found that inhibition by tentoxin caused a virtually complete stop of rotation, which was partially relieved at higher tentoxin concentrations. Re-activation, however, was not simply a reversal of inhibition; while the torque appears unaffected as compared with the situation without tentoxin, F 1 under re-activating conditions was less susceptible to inhibitory ADP binding but displayed a large number of short pauses, indicating infringed energy conversion.F 1 -ATPase, the water-soluble part of F o F 1 -ATP synthase, splits ATP into ADP and inorganic phosphate (1, 2). The enzyme is found ubiquitously in bacteria, mitochondria, and chloroplasts and consists of five different subunits with a stoichiometry of ␣ 3 ␤ 3 ␥␦⑀. Its ␣ 3 ␤ 3 ␥ subcomplex is the minimal assembly capable of continuous hydrolysis of ATP. The ␣ and ␤ subunits, arranged in an alternating manner like the elements of an orange, form a hexagon with the ␥ subunit in its center (3). Rotation of the ␥ subunit within the ␣ 3 ␤ 3 ␥ hexagon during

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Tentoxin An uncompetitive inhibitor of lettuce chloroplast coupling factor 1

Cited by 52 publications

References 14 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

Catalytic Properties and Sensitivity to Tentoxin of Chlamydomonas reinhardtii ATP Synthases Changed in Codon 83 of atpB by Site-directed Mutagenesis

Complete Inhibition and Partial Re-activation of Single F1-ATPase Molecules by Tentoxin

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