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

A mini review of the properties of the natural phytotoxin, tentoxin, is proposed. In particular, the biological activities of tentoxin on the chloroplast F0F1 proton ATPase, which realizes the synthesis of ATP at the expense of an electrochemical gradient of protons, are discussed. In this respect, structure-activity relationships of tentoxin have been re-examined in the light of the recent developments obtained by two-dimensional proton nuclear magnetic resonance (81). The conformations of the cyclic tetrapeptide [cyclo-(L-MeAla1-L-Leu2-MePhe[(Z) delta]3-Gly4)] have been studied in aqueous solution at various temperatures. Contrary to what was observed in early studies in chloroform, tentoxin was proved to exhibit multiple exchanging conformations in water. Four conformations with different proportions (51, 37, 8 and 4%) were found. Models were derived from nuclear magnetic resonance parameters and restrained molecular dynamics simulations. They confirmed that the four conformers exhibited the cis-trans-cis-trans configuration of the amide bond sequence. The conversion from one form to another is accomplished by a conformational peptide flip consisting of a 180 degrees rotation of a non-methylated peptide bond. In addition, important aggregation phenomena were observed. These effects have also been evidenced in chloroform, and compared to results derived from experiments carried out in the presence of DPC micelles. The tentoxin molecule was found self-associated in solution in a micellar-like organization. On the basis of these observations, we propose to design new analogues, with the intention of elucidating the mode of action of tentoxin in plants on the molecular level, especially under the aspect of its interaction with the chloroplast ATPase.
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PMID:[Tentoxin: structure-activity relationship. Application to the study of its action on chloroplast ATP-synthase]. 929 66

Eight synthetic analogues of tentoxin (cyclo-(L-N-MeGlu1-L-Leu2-N-MeDeltaZPhe3-Gly4)) modified in residues 1, 2, and 3 were checked for their ability to inhibit and reactivate the ATPase activity of the activated soluble part of chloroplast ATP synthase. The data were consistent with a model involving two binding sites of different affinities for the toxins. The occupancy of the high affinity site (or tight site) gave rise to an inactive complex, whereas filling both sites (tight + loose) gave rise to a complex of variable activity, dependent on the toxin analogue. Competition experiments between tentoxin and nonreactivating analogues allowed discrimination between the absence of binding and a nonproductive binding to the site of lower affinity (or loose site). The affinity for the loose site was not affected significantly by the modifications of the tentoxin molecule, whereas the affinity for the tight site was found notably changed. Increasing the size of side chain 1 or 2 and introducing a net electrical charge both resulted in a decrease of affinity for the tight site, but the second change dominated the first one. The activity of different ternary complexes enzyme-tentoxin-analogue depended on the nature of the toxin bound on each site and not only on that bound on the loose site. This demonstrates that the reactivation process results from an interaction, direct or not, between these two binding sites. Possible molecular mechanisms are discussed.
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PMID:Interrelation between high and low affinity tentoxin binding sites in chloroplast F1-ATPase revealed by synthetic analogues. 945 52