Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Two catalytic structures of H(+)-motive ATP synthase (Fig. 1), the alpha 3 beta 3 oligomer (M(r) = 319,581) and alpha 1 beta 1 promoter (M(r) = 106,527) (Fig. 2), were isolated using high pressure liquid chromatography (Fig. 3) and polyacrylamide gel electrophoresis (Figs. 4 and 5). These were reconstituted from the alpha and beta subunits of thermophilic F1 (TF1), and the alpha 3 beta 3 oligomer was also crystallized. Common to both F1 and the alpha 3 beta 3 oligomer were the nucleotide specificity, the two Km values, the presence of protomer-oligomer activities, and the one-hit--one-kill phenomenon. A synchrotron experiment on the ATP hydrolysis cycle revealed the dynamic shrinkage and expansion of F1(44) that correspond, respectively, to the ATP-induced association and ADP-induced dissociation of the alpha 3 beta 3 oligomer. The oligomer, like mitochondrial F1 and TF1, exhibited two kinds of ATPase activity: one was cooperative and was inhibited by only one inhibitor per hexamer, and the other was inhibited by three inhibitors per hexamer.
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PMID:The alpha 3 beta 3 and alpha 1 beta 1 complexes of ATP synthase. 128 33

The basic structures of the catalytic portion (F1, alpha 3 beta 3 gamma delta epsilon) of ATP synthase are the alpha 3 beta 3 hexamer (oligomer with cooperativity) and alpha 1 beta 1 heterodimer (protomer). These were reconstituted from the alpha and beta subunits of thermophilic F1 (TF1), and the alpha 3 beta 3 hexamer was crystallized. On electrophoresis, both the dimer and hexamer showed bands with ATPase activity. Using the dimer and hexamer, we studied the nucleotide-dependent rapid molecular dynamics. The formation of the hexamer required neither nucleotide nor Mg. The hexamer was dissociated into the dimer in the presence of MgADP, while the dimer was associated into the hexamer in the presence of MgATP. The hexamer, like mitochondrial F1 and TF1, showed two kinds of ATPase activity: one was cooperative and was inhibited by only one BzADP per hexamer, and the other was inhibited by three BzADP per hexamer.
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PMID:The alpha beta complexes of ATP synthase: the alpha 3 beta 3 oligomer and alpha 1 beta 1 protomer. 142 37

Studies with a synthetic presequence peptide, F1 beta 1-20, corresponding to the NH2-terminal 20 amino acids of the F1-ATPase beta-subunit precursor (pF1 beta) show that although this peptide binds avidly to phospholipid bi-layers it does not efficiently compete for import of full-length precursor into mitochondria, Ki approximately 100 microM (Hoyt, D.W., Cyr, D.M., Gierasch, L.M., and Douglas, M.G. (1991) J. Biol. Chem. 266, 21693-21699). Herein we report that longer F1 beta presequence peptides F1 beta 1-32 + 2, F1 beta 1-32SQ + 2, and F1 beta 21-51 + 3 compete for mitochondrial import at 1000-, 250-, and 25-fold lower concentrations, respectively, than F1 beta 1-20. A longer peptide, F1 beta 1-51 + 3, was no more effective as an import competitor than F1 beta 1-32 + 2. Both minimal length and amphiphilic character appear required in order for F1 beta peptides to block mitochondrial import. Import competition by longer F1 beta peptides seems to occur at a step common to all precursors since they blocked import of precursors to F1-ATPase alpha- and beta-subunits and the ADP/ATP carrier protein. Dissipation of membrane potential (delta psi) across the inner mitochondrial membrane is observed in the presence of F1 beta-peptides, but this mechanism alone does not account for the observed import inhibition. F1 beta 1-32 + 2 and 21-51 + 3 block import of pF1 beta 100% at peptide concentrations which dissipate delta psi less than 25%. In contrast, experiments with valinomycin demonstrate that when mitochondrial delta psi is reduced 25% import of pF1 beta is inhibited only 25%. Therefore, at least 75% of maximal import inhibition observed in the presence of F1 beta 1-32 + 2 and F1 beta 21-51 + 3 does not result from dissipation of delta psi. Import inhibition by F1 beta-peptides is reversible and can be overcome by increasing the amount of full-length precursor in import reactions. F1 beta presequence peptides and full-length precursor are therefore likely to compete for a common import step. Presequence dependent binding of pF1 beta to trypsin-sensitive elements on the outer mitochondrial membrane is insensitive to inhibitory concentrations of F1 beta presequence peptide. We conclude that import inhibition by F1 beta presequence peptides is competitive and occurs at a site beyond initial interaction of precursor proteins with mitochondria.
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PMID:Early events in the transport of proteins into mitochondria. Import competition by a mitochondrial presequence. 183 61

The alpha 3 beta 3 hexamer was reconstituted from the alpha and beta subunits of TF1 portion of ATP synthase of thermophilic bacterium (Kagawa et al. (1989) FEBS Lett. 249, 67). The alpha 1 beta 1 heterodimer of ATP synthase was isolated by high performance liquid chromatography (HPLC) of the alpha 3 beta 3 hexamer in the presence of AT(D)P-Mg. On polyacrylamide gel electrophoresis, both bands corresponding to the dimer and hexamer showed ATPase activity. The alpha 1 beta 1 dimer was dissociated into the equal amounts of the alpha and beta monomers by sodium dodecyl sulfate. The alpha and beta monomers were practically inactive. The alpha 2 and beta 2 homodimers were not detected by electrophoresis and HPLC.
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PMID:The alpha 1 beta 1 heterodimer of ATP synthase. 214 34

Digestion of the F1-ATPase of Escherichia coli with trypsin stimulated ATP hydrolytic activity and removed the delta and epsilon subunits of the enzyme. A species represented by the formula alpha 1(3) beta 1(3) gamma 1, where alpha 1, beta 1 and gamma 1 are forms of the native alpha, beta and gamma subunits which have been attacked by trypsin, was formed by trypsin digestion in the presence of ATP. In the presence of ATP and MgCl2, conversion of gamma to gamma 1 was retarded and the enzyme retained the epsilon subunit. These results imply that binding of ATP to the beta subunits alters the conformation of ECF1 to increase the accessibility of the gamma subunit to trypsin. The likely trypsin cleavage sites in the alpha, beta and gamma subunits are discussed. ECF1 from the alpha subunit-defective mutant uncA401, or after treatment with N,N'-dicyclohexylcarbodiimide or 4-chloro-7-nitrobenzofurazan, was present in a conformation in which the gamma subunit was readily accessible to trypsin and could not be protected by the presence of ATP and MgCl2. In a similar manner to native E. coli F1-ATPase, the hydrolytic activity of the trypsin-digested enzyme was stimulated by the detergent lauryldimethylamine N-oxide. Since the digested enzyme lacked the epsilon subunit, a putative inhibitor of hydrolytic activity, a mechanism for the stimulation which involves loss or movement of this subunit is untenable.
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PMID:Ligand-induced conformational changes in the Escherichia coli F1 adenosine triphosphatase probed by trypsin digestion. 289 Mar 77

Inferred from the crystal structure of mitochondrial F1-ATPase (Abrahams, J.P. et al. (1994) Nature 370, 621-628), the proteinase-sensitive region around Phe-395 of thermophilic F1-ATPase alpha-subunit corresponds to the loop which connects main part of the carboxyl-terminal helical bundle domain with the ATP binding domain. This loop is in contact with the gamma- and adjacent beta-subunits. Two polypeptides corresponding to the sequence 1-395 and 396-503 of the alpha-subunit were expressed in Escherichia coli cells and they were copurified as an apparently functional alpha-subunit (alpha(395/396)) made up of two polypeptides. The isolated alpha(395/396) was stabilized by ATP-Mg, but not by ADP-Mg, although it bound both ATP-Mg and ADP-Mg with similar affinities (Kd, 11 microM and 14 microM, respectively). The alpha(395/396) was reconstitutable into alpha(395/396)3 beta 3 and alpha(395/396)3 beta 3 gamma complexes. Different from the intact the ATP-Mg-induced dissociation into alpha 1 beta 1 heterodimers. ATP hydrolysis by the alpha(395/396)3 beta 3 gamma complex underwent a slow initial phase, whereas the intact alpha 3 beta 3 gamma complex exhibited an accelerated initial phase. Steady-state ATPase activity at various ATP concentrations showed negative cooperativity for the intact alpha 3 beta 3 gamma complex but apparently positive cooperativity for the alpha(395/396)3 beta 3 gamma complex. The ATPase activities at a saturating ATP concentration of the complexes containing the alpha(395/396) were 180% of those containing intact alpha-subunits. These results indicate that a loop around Phe-395 is involved in intersubunit interaction in F1-ATPase.
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PMID:F1-ATPase alpha-subunit made up from two fragments (1-395, 396-503) is stabilized by ATP and complexes containing it obey altered kinetics. 772 99

The ATP-hydrolyzing excitation state of the alpha 3 beta 3 complex of the ATP synthase from the thermophilic bacterium PS3 was investigated using time-resolved small-angle X-ray scattering with synchrotron radiation. The results showed the presence of the alpha 3 beta 3 complex at a steady state during ATP hydrolysis when the alpha 3 beta 3 hexamer reacted with Mg-ATP. The radius of gyration of the complex in the steady state was significantly larger than that of the Mg-AMP-PNP-hexamer complex, indicating a conformational change to an expanded structure during catalysis. This alpha 3 beta 3 complex dissociated into alpha 1 beta 1 heterodimers with apparent first-order reaction kinetics after all the ATPs were converted to ADPs. In contrast, when the alpha 3 beta 3 complex reacted with Mg-ADP, the complex dissociated into dimers with apparent first-order reaction kinetics without showing the steady state of the complex. The dimers, however, re-associated into the hexamer when Mg-ATP was added. The results were well-explained by a computer simulation based on non-linear chemical dynamics, in which a reaction mechanism that incorporates the dynamic structure of the hexamer in the steady state was considered.
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PMID:ATP-hydrolyzing excitation state of the reconstituted alpha 3 beta 3 complex of ATP synthase from the thermophilic bacterium PS3: structural characteristics shown by time-resolved small-angle X-ray scattering with synchrotron radiation. 777 76

A protocol was designed to obtain a pure fraction of pollen mitochondria from the diploid species Nicotiana sylvestris, the female parent of the allotetraploid Nicotiana tabacum. Most organelles were morphologically intact and able to perform in organello mitochondrial (mt) protein synthesis. As revealed by two-dimensional protein electrophoresis, numerous quantitative differences exist between leaf and pollen mt proteins. Moreover, additional mt polypeptides, named R (for reproductive), encoded by either nuclear or mitochondrial genes, are found in pollen. The most abundant R polypeptide, R1 (M(r) 53,000, pI 5.6), is nuclearly encoded, is membrane bound, and cross-reacts with an antibody directed against the beta subunit of the mt ATP synthase (ATPase). N-terminal microsequence analysis showed that the two ATPase beta subunits present in leaves (beta 1 and beta 2) and the R1 pollen-specific subunit are encoded by distinct genes. A similar additional ATPase beta subunit was observed in pollen mitochondria from Petunia, suggesting that this polypeptide is of general importance for male gametophytic development in Solanaceaes.
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PMID:Specific mitochondrial proteins in pollen: presence of an additional ATP synthase beta subunit. 832 63

AT(D)PMg induces dissociation of the alpha 3 beta 3 complex of F1-ATPase from a thermophilic Bacillus strain. PS3, into the alpha 1 beta 1 heterodimers [(1991) Biochim. Biophys. Acta 1056, 279-284] but the location of the AT(D)PMg binding site responsible is not known. From the analysis of AT(D)PMg binding properties of the isolated mutant beta subunit, beta(Y341C), and the stability of the alpha 3 beta(Y341C)3 complex in the presence of AT(D)PMg, we conclude that binding of AT(D)PMg to the Tyr-341 site of the beta subunit(s) in the alpha 3 beta 3 complex triggers the dissociation of the alpha 3 beta 3 complex into the alpha 1 beta 1 heterodimers.
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PMID:AT(D)PMg-induced dissociation of the alpha 3 beta 3 complex of the F1-ATPase from a thermophilic Bacillus PS3 into alpha 1 beta 1 heterodimers is prevented by mutation beta (Y341C). 846 9

We have previously demonstrated that epidermal growth factor (EGF), colony stimulating factor-1 (CSF-I), and granulocyte-monocyte colony stimulating factor (GMCSF) stimulate, while transforming growth factor beta 1 (TGF beta 1) inhibits, cytotrophoblast differentiation. To identify genes mediating EGF induced differentiation, we constructed a subtracted cDNA library between undifferentiated cytotrophoblast and differentiating cytotrophoblast. We identified six novel genes and four known syncytial products alpha-human chorionic gonadotrophin (alpha hCG) pregnancy-specific beta 1-glycoprotein, 3 beta-hydroxysteroid dehydrogenase, and plasminogen activator inhibitor type 1 whose mRNAs increased during differentiation. Ten other genes were identified whose mRNAs increased during differentiation. Five of these (keratin 19, calcreticulin, heat shock protein 27, serum and glucocorticoid-regulated kinase and adrenomedullin) were not previously reported to be expressed in placenta. Five other genes known to be expressed in placenta were identified. keratin 8, fibronectin, mitochondrial ATP synthase, 1119, and cytosolic copper-zinc superoxide dismutase (SOD-1). Several of these genes may have regulatory functions in trophoblast differentiation.
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PMID:Identification by subtractive hybridization of a spectrum of novel and unexpected genes associated with in vitro differentiation of human cytotrophoblast cells. 889 72


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