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)

Oligomycin sensitivity conferral protein, in the absence of coupling factor 6 (F6), is able to bind the ATPase to mitochondrial membranes with an apparent association constant of 10(6) M-1. The F6-dependent ATPase binding has an apparent association constant 1 to 2 orders of magnitude lower than that obtained with oligomycin sensitivity conferral protein. The oligomycin sensitivity conferral protein-dependent, membrane-bound ATPase activity is sensitive to rutamycin while the F6-dependent, membrane-bound ATPase activity is insensitive to rutamycin. F1-ATPase and Type II ATPase require F6 in addition to oligomycin sensitivity conferral protein and FB to reconstitute 32Pi-ATP exchange activity in silicotungstic acid particles. This F6 requirement for the 32Pi-ATP exchange is not related to the F6 effect on the ATPase binding. The Type I ATPase and therefore the 26,500-dalton subunit associated with it requires F6 and FB to reconstitute 32Pi-ATP exchange activity in silicotungstic acid particles. Oligomycin sensitivity conferral protein can be interchanged with the 26,500-dalton ATPase binding protein in the binding of the ATPase and the 32Pi-ATP exchange.
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PMID:Subunit interaction in the mitochondrial H+-translocating ATPase. The role of oligomycin sensitivity conferral protein and coupling factor 6 in ATPase binding and Pi-ATP exchange in mitochondrial membranes. 613 98

This review concerns the catalytic sector of F1 factor of the H+-dependent ATPases in mitochondria (MF1), bacteria (BF1) and chloroplasts (CF1). The three types of F1 have many similarities with respect to the structural parameters, subunit composition and catalytic mechanism. An alpha 3 beta 3 gamma delta epsilon stoichiometry is now accepted for MF1 and BF1; the alpha 2 beta 2 gamma 2 delta 2 epsilon 2 stoichiometry for CF1 remains as matter of debate. The major subunits alpha, beta and gamma are equivalent in MF1, BF1 and CF1; this is not the case for the minor subunits delta and epsilon. The delta subunit of MF1 corresponds to the epsilon subunit of BF1 and CF1, whereas the mitochondrial subunit equivalent to the delta subunit of BF1 and CF1 is probably the oligomycin sensitivity conferring protein (OSCP). The alpha beta gamma assembly is endowed with ATPase activity, beta being considered as the catalytic subunit and gamma as a proton gate. On the other hand, the delta and epsilon subunits of BF1 and CF1 most probably act as links between the F1 and F0 sectors of the ATPase complex. The natural mitochondrial ATPase inhibitor, which is a separate protein loosely attached to MF1, could have its counterpart in the epsilon subunit of BF1 and CF1. The generally accepted view that the catalytic subunit in the different F1 species is beta comes from a number of approaches, including chemical modification, specific photolabeling and, in the case of BF1, use of mutants. The alpha subunit also plays a central role in catalysis, since structural alteration of alpha by chemical modification or mutation results in loss of activity of the whole molecule of F1. The notion that the proton motive force generated by respiration is required for conformational changes of the F1 sector of the H+-ATPase complex has gained acceptance. During the course of ATP synthesis, conversion of bound ADP and Pi into bound ATP probably requires little energy input; only the release of the F1-bound ATP would consume energy. ADP and Pi most likely bind at one catalytic site of F1, while ATP is released at another site. This mechanism, which underlines the alternating cooperativity of subunits in F1, is supported by kinetic data and also by the demonstration of partial site reactivity in inactivation experiments performed with selective chemical modifiers. One obvious advantage of the alternating site mechanism is that the released ATP cannot bind to its original site.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Recent developments on structural and functional aspects of the F1 sector of H+-linked ATPases. 623 69

The purified, soluble F1-ATPase was modified by several covalently reacting inhibitors, either known or considered to bind to the active site bearing beta-subunit, to cause partial inhibition up to 99%. The modified enzyme was then reconstituted in the presence of OSCP (oligomycin sensitivity conferring protein) with submitochondrial particles (SMP) almost completely (greater than 99%) denuded of active F1-ATPase and was assayed for oligomycin-sensitive ATPase and oxidative phosphorylation activities. The inhibitors used were 1-fluoro-2,4-dinitrobenzene (FDNB), N-(ethoxycarbonyl)-2-ethoxy-1,2-dihydroquinoline (EEDQ), 1-cyclohexyl-3-(2-morpholinoethyl)carbodiimide metho-p-toluenesulfonate (CMCD), quinacrine mustard (QM), 5-(dimethylamino)-naphthalene-1-sulfonyl chloride (dansyl-Cl), 5'-[p-(fluoro-sulfonyl)benzoyl]adenosine (FSBA), and N,N'-dicyclohexylcarbodiimide (DCCD). The SMP reconstituted with unmodified F1 exhibited oxidative phosphorylation and oligomycin-sensitive ATPase (in the presence of uncouplers) activities as high as 500 nmol min-1 mg-1 and 8 mumol min-1 mg-1, respectively. The systems reconstituted with F1 modified to cause various degrees of inhibition with FDNB, EEDQ, CMCD, QM, and dansyl-Cl exhibited the same degree of inhibition of oxidative phosphorylation and oligomycin-sensitive ATPase activities as the inhibition of the ATPase activity of the modified F1 before reconstitution. The systems reconstituted with FSBA-modified F1 showed the following relative degrees of inhibition: oxidative phosphorylation greater than oligomycin-sensitive ATPase of particles greater than ATPase of soluble F1. In contrast, the systems reconstituted with DCCD-modified F1 showed much greater inhibition of oligomycin-sensitive ATPase than of oxidative phosphorylation activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibitory chemical modifications of F1-ATPase: effects on the kinetics of adenosine 5'-triphosphate synthesis and hydrolysis in reconstituted systems. 623 51

Polyacrylamide gel electrophoresis in the presence of a cationic detergent, tetradecyltrimethylammonium bromide (TDAB) has been compared to electrophoresis in the presence of an anionic detergent, sodium dodecyl sulfate (SDS). Although, in both systems, the peptides generally migrated as a function of their molecular weight, the TDAB electrophoresis permitted us to obtain a much better resolution of several peptides of the mitochondrial F0-F1-ATPase, especially for the alpha and beta subunits and for the oligomycin sensitivity conferring protein (OSCP). The differences between the two electrophoretic profiles have been used to devise a new technique of two-dimensional electrophoresis using successively anionic and cationic detergents. This method could be very useful in the case of membrane proteins, which are generally soluble only in the presence of powerful ionic detergents. It has been particularly successful in resolving the small peptides of the F0-F1-ATPase which were difficult to differentiate by other techniques in one- or two-dimensional polyacrylamide gel electrophoresis.
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PMID:Two-dimensional gel electrophoresis of membrane proteins using anionic and cationic detergents. Application to the study of mitochondrial F0-F1-ATPase. 623 56

Mitochondrial ATPase inhibitor protein (IF1) reacts reversibly with complex V and inhibits up to 90% of its ATPase activity. Both the rate and extent of inhibition are pH and temperature dependent and increase as the pH is lowered from pH 8 tp 6.7 (the lowest pH examined) or as the temperature is increased from 4 to 36 degrees C. Nucleotide triphosphates plus Mg2+ ions are required for inhibition of complex V ATPase activity by IF1. In the presence of Mg2+ ions, the effectiveness order of nucleotides is ATP greater than ITP greater than GTP greater than UTP. Highly purified complex V, which requires added phospholipids for expressing ATPase and ATP-Pi exchange activities, cannot be inhibited by IF1 plust ATP-Mg2+ unless phospholipids are also added. This indicates that the active state of the enzyme is necessary for the IF1 effect to be manifested, because F1-ATPase, which does not contain nor require phospholipids for catalyzing ATP hydrolysis, can be inhibited by IF1 plus ATP-Mg2+ in the absence of added phospholipids. The IF1-inhibited complex V, but not IF1-inhibited F1-ATPase, can be reactivated by incubation at pH greater than 7.0 in the absence of ATP-Mg2+. The reactivation rate is pH dependent and is influenced by temperature and enzyme concentration. Complex V preparations contain small and variable amounts of IF1. This endogenous IF1 behaves the same as added IF1 with respect to conditions described above for inhibition and reactivation and can result in 25-50% inhibition in different complex V preparations. However, complex V lacking endogenous IF1 can be reconstituted from F0, F1, oligomycin sensitivity conferring protein, and phospholipids. Inhibition of this reconstituted preparation in the presence of ATP-Mg2+ depends entirely on addition of IF1. In general, the ATP-Pi exchange activity of complex V is more sensitive to the chemical inhibitors of F1-AtPase tha its ATPase activity. This is not so, however, for IF1. Under conditions that IF1 caused approximately 75% inhibition of ATPase activity of complex V, no more than 10% of the ATP-Pi exchange activity was inhibited.
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PMID:Mitochondrial adenosinetriphosphatase inhibitor protein: reversible interaction with complex V (ATP synthetase complex). 626 16

Three apparently different modifications of submitochondrial particles (SMP) or ATP synthase preparations (complex V) inhibit oxidative phosphorylation and ATP-32Pi exchange activities, all of which are reversible by addition of mono- or dithiols. (a) Triphenyltin chloride inhibits ATP synthesis and hydrolysis without uncoupling. The inhibition by triphenyltin chloride is reversible by addition of beta-mercaptoethanol, dithiothreitol, or dihydrolipoamide. (b) Factor B is a water-soluble protein of Mr (11-12) X 10(3), contains a vicinal dithiol, and is required for energy transfer to and from F1-ATPase when tested with SMP-rendered factor B deficient by extraction with ammonia-ethylenediaminetetraacetic acid (EDTA) (AE-SMP). Treatment of factor B with mono- and dithiol modifiers, such as p-(chloromercuri)benzenesulfonate (PCMPS), Cd2+, or diazenedicarboxylic acid bis(dimethylamide) (diamide), inhibits factor B. This inhibition is reversed by addition to modified factor B of appropriate mono- and dithiol compounds. Preparations of AE-SMP are partially F1 deficient and partially uncoupled. The uncoupling can be repaired completely by addition of factor B or low levels of oligomycin, or to a large extent by addition of F1-ATPase + oligomycin sensitivity conferring protein. (c) SMP, AE-SMP, and complex V can be completely uncoupled by treatment at 30 degrees C with phenylarsine oxide, Cd2+, diamide, PCMPS, monobromobimane, and mono- and bifunctional maleimides. The uncoupling by these reagents is potentiated by membrane energization. Uncoupling by diamide is greater than or equal to 80% reversed by dihydrolipoamide or beta-mercaptoethanol, the former being much more potent. Dithiothreitol and dithioerythritol are poorly effective.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Thiols in oxidative phosphorylation: inhibition and energy-potentiated uncoupling by monothiol and dithiol modifiers. 647 76

Exon trapping was used to clone portions of potential genes from human chromosome 21. One trapped sequence showed striking homology with the bovine and rat ATP synthase OSCP (oligomycin sensitivity conferring protein) subunit. We subsequently cloned the full-length human ATP synthase OSCP cDNA (GDB/HGMW approved name ATP50) from infant brain and muscle libraries and determined its nucleotide and deduced amino acid sequence (EMBL/GenBank Accession No. X83218). The encoded polypeptide contains 213 amino acids, with more than 80% identity to bovine and murine ATPase OSCP subunits and over 35% identity to Saccharomyces cerevisiae and sweet potato sequences. The human ATP5O gene is located at 21q22.1-q22.2, just proximal to D21S17, in YACs 860G11 and 838C7 of the Chumakov et al. (Nature 359:380, 1992) YAC contig. The gene is expressed in all human tissues examined, most strongly in muscle and heart. This ATP5O subunit is a key structural component of the stalk of the mitochondrial respiratory chain F1F0-ATP synthase and as such may contribute in a gene dosage-dependent manner to the phenotype of Down syndrome (trisomy 21).
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PMID:Cloning of the cDNA for the human ATP synthase OSCP subunit (ATP5O) by exon trapping and mapping to chromosome 21q22.1-q22.2. 749 82

The oligomycin sensitivity conferring protein (OSCP) of Saccharomyces cerevisiae is a component of the stalk FA sector of the mitochondrial F1Fo-ATP synthase complex (mtATPase). The subunits comprising this sector have been implicated in the coupling of proton flux through the membrane Fo sector to ATP synthesis on the catalytic F1 sector. We tested whether the yeast subunit encoded by the ATP5 gene could be functionally replaced by a mammalian homologue, rat OSCP. The yeast and rat OSCP proteins have 58% homology in terms of conserved amino acids. A vector-borne rat cDNA encoding the OSCP precursor was introduced into a yeast strain lacking endogenous OSCP as a result of its disrupted ATP5 gene. The resultant yeast cells showed essentially a wildtype growth rate at 18, 28 and 35 degrees C, on nonfermentable substrates. Expression of mammalian FA subunit homologues in yeast should provide a productive new approach to generating information on the structure and function of mtATPase.
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PMID:The functional expression of a rat cDNA encoding OSCP in the yeast Saccharomyces cerevisiae. 786 99

We have postulated that magnesium may play a role in altering the lipid fluidity of the bilayers, which would induce a change of conformation of the F0-ATPase portion (buried in the lipid core) of mitochondrial F0-F1-ATPase. Such change could be transmitted to the soluble F1 portion, resulting in higher enzymatic activity. The assumption was further supported by the results presented in the following: (1) A conformational difference for the F0-ATPase-containing proteoliposomes induced by the magnesium effect could be detected using a fluorescent probe acrylodan; (2) H(+)-translocation activity of F0-ATPase-incorporated proteoliposomes with magnesium, monitoring by fluorescence quenching of 9-aminoacridine or the bulk phase pH change, was higher than that without magnesium; (3) The magnesium effect on the reconstituted F0-F1-ATPase activity was greatly enhanced when the reconstitution was carried out in the presence of oligomycin sensitivity conferring protein (OSCP, a main component of the connecting link between the F1 and F0 sector of F0-F1-ATPase).
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PMID:Further study on the magnesium-mediated change in physical state of phospholipid modulates mitochondrial F0-F1-ATPase activity. 815 82

Four cDNAs for the import precursors of oligomycin sensitivity conferring protein (OSCP), ATPase inhibitor protein (IF1) and subunit cs (encoded by P1 and P2 genes) of rat mitochondrial H(+)-ATP synthase have been cloned from a rat cDNA library. The import precursors and the mature polypeptides of rat OSCP, IF1, subunit c (P1) and subunit c (P2) consisted of 23/190, 25/82, 61/75 and 66/75 amino acids, respectively.
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PMID:Molecular cloning and sequence of cDNAs for the import precursors of oligomycin sensitivity conferring protein, ATPase inhibitor protein, and subunit c of H(+)-ATP synthase in rat mitochondria. 844 8


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