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:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dependence on the membrane lipids of sarcolemmal structure as well as functions was examined by incubating isolated rat heart sarcolemma with phospholipase A, C, or D. Conventional as well as negatively stained electron microscope preparations of the treated membranes revealed structural changes. Ca2+ binding and Na+, K+-ATPase activity were depressed following treatment of the membranes with any of the phospholipases whereas Ca2+-ATPase activity was not affected. Adenylate cyclase activity was increased by low concentration (25 micrograms/mg of protein) of phospholipase A, and a definite inhibition of the enzyme was noticed when the concentration of the phospholipase A was increased to 250 micrograms/mg of protein. Phospholipases C and D had no significant effect on the adenylate cyclase activity. Percentage of phospholipids hydrolyzed was more after phospholipase A treatments. These results provide evidence regarding the involvement of lipids in the membrane structure and functions.
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PMID:Structure-function relationship in heart sarcolemma. 739 39

The requirements for the DNA replication of the human papovavirus JC were analyzed using JC T-antigen as well as the T-antigens of the related viruses SV40 and BK. With all three T-antigens, the boundary of the core origin mapped on the early side to position 5093 of the viral genome. In conjunction with earlier studies, the core origin of DNA replication was therefore defined as a 68-bp region which, similar to the SV40 core origin, contains three major structural elements, early palindrome, T-antigen binding site II, and A/T-rich tract. Replication was stimulated by sequences flanking the core origin on the early side. Specifically, the stimulating sequences on the early side were identified as T-antigen binding site I. The degree to which flanking sequences were able to stimulate viral DNA replication was dependent on the T-antigen used in the experiment, with JC T-antigen relying most and BK T-antigen relying least on the flanking sequences. SV40 T-antigen showed an intermediate dependence. The same hierarchy was observed when replication activities were compared. BK T-antigen was more active in replicating DNA than SV40 T-antigen, which in turn was more effective than JC T-antigen. Dependence on flanking sequences is, thus, inversely correlated to the replicating activity of the respective T-antigen, showing that, in addition to the origin, the T-antigen contributes to the characteristics of JC virus DNA replication.
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PMID:Large T-antigen and sequences within the regulatory region of JC virus both contribute to the features of JC virus DNA replication. 824 77

In smooth muscle, release via the inositol 1,4,5-trisphosphate (Ins(1,4,5)P(3)R) and ryanodine receptors (RyR) on the sarcoplasmic reticulum (SR) controls oscillatory and steady-state cytosolic Ca(2+) concentrations ([Ca(2+)](c)). The interplay between the two receptors, itself determined by their organization on the SR, establishes the time course and spatial arrangement of the Ca(2+) signal. Whether or not the receptors are co-localized or distanced from each other on the same store or whether they exist on separate stores will significantly affect the Ca(2+) signal produced by the SR. To date these matters remain unresolved. The functional arrangement of the RyR and Ins(1,4,5)P(3)R on the SR has now been examined in isolated single voltage-clamped colonic myocytes. Depletion of the ryanodine-sensitive store, by repeated application of caffeine, in the presence of ryanodine, abolished the response to Ins(1,4,5)P(3), suggesting that Ins(1,4,5)P(3)R and RyR share a common Ca(2+) store. Ca(2+) release from the Ins(1,4,5)P(3)R did not activate Ca(2+)-induced Ca(2+) release at the RyR. Depletion of the Ins(1,4,5)P(3)-sensitive store, by the removal of external Ca(2+), on the other hand, caused only a small decrease ( approximately 26%) in caffeine-evoked Ca(2+) transients, suggesting that not all RyR exist on the common store shared with Ins(1,4,5)P(3)R. Dependence of the stores on external Ca(2+) for replenishment also differed; removal of external Ca(2+) depleted the Ins(1,4,5)P(3)-sensitive store but caused only a slight reduction in caffeine-evoked transients mediated at RyR. Different mechanisms are presumably responsible for the refilling of each store. Refilling of both Ins(1,4,5)P(3)-sensitive and caffeine-sensitive Ca(2+) stores was inhibited by each of the SR Ca(2+) ATPase inhibitors thapsigargin and cyclopiazonic acid. These results may be explained by the existence of two functionally distinct Ca(2+) stores; the first expressing only RyR and refilled from [Ca(2+)](c), the second expressing both Ins(1,4,5)P(3)R and RyR and dependent upon external Ca(2+) for refilling.
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PMID:Functionally separate intracellular Ca2+ stores in smooth muscle. 1147 79

The GHKL phosphotransferase superfamily, characterized by four sequence motifs that form the ATP-binding site, consists of the ATPase domains of type II DNA topoisomerases, Hsp90, and MutL, and bacterial and mitochondrial protein kinases. In addition to a magnesium ion, which is essential for catalysis, a potassium ion bound adjacent to the triphosphate moiety of ATP in a rat mitochondrial protein kinase, BCK (branched-chain alpha-ketoacid dehydrogenase kinase), has been shown to be indispensable for nucleotide binding and hydrolysis. Using X-ray crystallographic, biochemical, and genetic analyses, we find that the monovalent cation-binding site is conserved in MutL, but both Na(+) and K(+) support the MutL ATPase activity. When Ala100 of MutL is substituted by proline, mimicking the K(+)-binding environment in BCK, the mutant MutL protein becomes exclusively dependent on Na(+) for the ATPase activity. The coordination of this Na(+) ion is identical to that of the K(+) ion in BCK and involves four carbonyl oxygen atoms emanating from the hinges of the ATP lid and a non-bridging oxygen of the bound nucleotide. A similar monovalent cation-binding site is found in DNA gyrase with additional coordination by a serine side chain. The conserved and protein-specific monovalent cation-binding site is unique to the GHKL superfamily and probably essential for both ATPase and kinase activity. Dependence on different monovalent cations for catalysis may be exploited for future drug design specifically targeting each individual member of the GHKL superfamily.
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PMID:Monovalent cation dependence and preference of GHKL ATPases and kinases. 1278 29

Dependence on mitochondrial membrane potential (deltapsim) of hydrogen peroxide formation of in situ mitochondria in response to inhibition of complex I or III was studied in synaptosomes. Blockage of electron flow through complex I by rotenone or that through complex III by antimycin resulted in an increase in the rate of H2O2 generation as measured with the Amplex red assay. Membrane potential of mitochondria was dissipated by either FCCP (250 nM) or DNP (50 microM) and then the rate of H2O2 production was followed. Neither of the uncouplers had a significant effect on the rate of H2O2 production induced by rotenone or antimycin. Inhibition of the F0F1-ATPase by oligomycin, which also eliminates deltapsim in the presence of rotenone and antimycin, respectively, was also without effect on the ROS formation induced by rotenone and only slightly reduced the antimycin-induced H2O2 production. These results indicate that ROS generation of in situ mitochondria in nerve terminals in response to inhibition of complex I or complex III is independent of deltapsim. In addition, we detected a significant antimycin-induced H2O2 production when the flow of electrons through complex I was inhibited by rotenone, indicating that the respiratory chain of in situ mitochondria in synaptosomes has a substantial electron influx distal from the rotenone site, which could contribute to ROS generation when the complex III is inhibited.
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PMID:The production of reactive oxygen species in intact isolated nerve terminals is independent of the mitochondrial membrane potential. 1457 Apr 3

We present evidence strongly suggesting that a proton gradient (acid inside) is used to drive an electroneutral, substrate-specific, K(+)/H(+) antiport in both tonoplast and plasma membrane-enriched vesicles obtained from oilseed rape (Brassica napus) hypocotyls. Proton fluxes into and out of the vesicles were monitored both by following the quenching and restoration of quinacrine fluorescence (indicating a transmembrane pH gradient) and of oxonol V fluorescence (indicating membrane potential.) Supply of K(+) (with Cl(-) or SCN(-)) after a pH gradient had been established across the vesicle membrane by provision of ATP to the H(+)-ATPase dissipated the transmembrane pH gradient but did not depolarize the positive membrane potential. Evidence that the K(+)/H(+) exchange thus indicated could not be accounted for by mere electric coupling included the findings that, first, no positive potential was generated when KSCN or KCl was supplied, even in the absence of 100 millimolar Cl(-) and, second, efflux of K(+) from K(+)-loaded vesicles drives intravesicular accumulation of H(+) against the electrochemical potential gradient. Neither was the exchange due to competition between K(+) and quinacrine for membrane sites, nor to inhibition of the H(+)-ATPase. Thus, it is likely that it was effected by a membrane component. The exchanger utilized primarily K(+) (at micromolar concentrations); Na(+)/H(+) antiport was detected only at concentrations two orders of magnitude higher. Rb(+), Li(+), or Cs(+) were ineffective. Dependence of tonoplast K(+)/H(+) antiport on K(+) concentration was complex, showing saturation at 10 millimolar K(+) and inhibition by concentrations higher than 25 millimolar. Antiport activity was associated both with tonoplast-enriched membrane vesicles (where the proton pump was inhibited by more than 80% by 50 millimolar NO(3) (-) and showed no sensitivity to vanadate or oligomycin) and with plasma membrane-enriched fractions prepared by phase separation followed by separation on a sucrose gradient (where the proton pump was vanadate and diethylstilbestrol-sensitive but showed no sensitivity to NO(3) (-) or oligomycin). The possible physiological role of such a K(+)/H(+) exchange mechanism is discussed.
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PMID:Evidence for a highly specific k/h antiporter in membrane vesicles from oil-seed rape hypocotyls. 1666 11

The effect of (mu(3)-diethylentriamino)-chloro-palladium(II)-chloride ([PdCl(dien)]Cl) on the activity of Na/K-ATPase from porcine cerebral cortex was studied in vitro, in the absence and presence of -SH containing ligands L-cysteine and glutathione (GSH). The aim of the study was to elucidate the mechanism of [PdCl(dien)](+) induced inhibition of the enzyme activity and to examine the ability of thiols to prevent and recover the inhibition. The coordinative interaction between [PdCl(dien)](+) and enzyme was verified by UV and (1)H NMR spectra. The semblance in the changes in absorption spectra of [PdCl(dien)](+) in the presence of Na/K-ATPase and thiols (L-cysteine and GSH) suggested that the complex ion interacts with enzymatic sulfhydryl groups. [PdCl(dien)](+) inhibited the enzyme activity in a dose-dependent manner. The Hill analysis of the inhibition curve yielded the half-maximum inhibitory activity value, IC(50)=1.21 x 10(-4)M, and Hill coefficient, n=0.7, suggesting the negative cooperation for binding of [PdCl(dien)](+) to the enzyme. Dependence of the initial reaction rate on the concentration of MgATP(2-) exhibited typical Michelis-Menten kinetics in the absence and presence of the inhibitor. Kinetic analysis showed that [PdCl(dien)](+) inhibited Na/K-ATPase by reducing the maximum reaction rate (V(max)), rather than changing the affinity to the substrate (K(m)). Kinetic parameters derived using Lineweaver-Burk transformation of experimental data indicated the non-competitive nature of Na/K-ATPase inhibition. The inhibitory constant, K(i)=1.05 x 10(-4)M, was determined from secondary replot of Lineweaver-Burk graph, and correlated with stability constants of [Pd(dien)(thiol)] complexes. 1 x 10(-3)M L-cysteine or GSH prevented the enzyme inhibition induced by Pd(II) complex cation when present below 1 x 10(-4)M. The both thiols completely reversed the inhibited activity in the concentration dependent manner, due to the complex formation with [PdCl(dien)](+).
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PMID:Prevention and recovery of (mu(3)-diethylentriamino)-chloro-palladium(II)-chloride induced inhibition of Na/K-ATPase by SH containing ligands--L-cysteine and glutathione. 1669 49

The benzothiazepine derivative K-201 has been suggested as a potential therapeutic agent due to its antiarrhythmogenic action. To understand how the drug alters calcium release from the sarcoplasmic reticulum (SR), we investigated its effects on the SR calcium channel and calcium pump by single channel electrophysiology, whole-cell confocal microscopy, and ATPase activity measurements on control and post-myocardial infarcted (PMI) rat skeletal muscle. In bilayers, K-201 induced two subconductance states corresponding to approximately 24% (S(1)) and approximately 13% (S(2)) of the maximum conductance. Dependence of event frequency and of time spent in S(1) and S(2) on the drug concentration was biphasic both in control and in PMI rats, with a maximum at 50 microM. At this concentration, the channel spends 26 +/- 4% and 24 +/- 4%, respectively, of the total time in these subconductance states at positive potentials, while no subconductances are observed at negative potentials. K-201 altered the frequency of elementary calcium release events: spark frequency decreased from 0.039 +/- 0.001 to 0.023 +/- 0.001 s(-1) sarcomere(-1), while the frequency of embers increased from 0.011 +/- 0.001 to 0.023 +/- 0.001 s(-1) sarcomere(-1). Embers with different amplitude levels were observed after the addition of the drug. K-201 inhibited the Ca(2+) ATPase characterized by IC(50,contr) = 119 +/- 21 muM and n (Hill,contr) = 1.84 +/- 0.48 for control and IC(50,PMI) = 122 +/- 18 microM and n (Hill,PMI) = 1.97 +/- 0.24 for PMI animals. These results suggest that although K-201 would increase the appearance of subconductance states, the overall calcium release is reduced by the drug. In addition, the effect of K-201 is identical on calcium release channels from control and PMI rats.
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PMID:Effects of K-201 on the calcium pump and calcium release channel of rat skeletal muscle. 1845 45

Glutamatergic neurotransmission accounts for a considerable part of energy consumption related to signaling in the brain. Chemical energy is provided by adenosine triphosphate (ATP) formed in glycolysis and tricarboxylic acid (TCA) cycle combined with oxidative phosphorylation. It is not clear whether ATP generated in these pathways is equivalent in relation to fueling of the energy-requiring processes, i.e., vesicle filling, transport, and enzymatic processing in the glutamatergic tripartite synapse (the astrocyte and pre- and postsynapse). The role of astrocytic glycogenolysis in maintaining theses processes also has not been fully elucidated. Cultured astrocytes and neurons were utilized to monitor these processes related to glutamatergic neurotransmission. Inhibitors of glycolysis and TCA cycle in combination with pathway-selective substrates were used to study glutamate uptake and release monitored with D-aspartate. Western blotting of glyceraldehyde-3-P dehydrogenase (GAPDH) and phosphoglycerate kinase (PGK) was performed to determine whether these enzymes are associated with the cell membrane. We show that ATP formed in glycolysis is superior to that generated by oxidative phosphorylation in providing energy for glutamate uptake both in astrocytes and in neurons. The neuronal vesicular glutamate release was less dependent on glycolytic ATP. Dependence of glutamate uptake on glycolytic ATP may be at least partially explained by a close association in the membrane of GAPDH and PGK and the glutamate transporters. It may be suggested that these enzymes form a complex with the transporters and the Na(+) /K(+) -ATPase, the latter providing the sodium gradient required for the transport process.
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PMID:Neuron-glia interactions in glutamatergic neurotransmission: roles of oxidative and glycolytic adenosine triphosphate as energy source. 2191 35

This paper represents H+ circles through the bacterial membranes, their peculiarities and relationship with ATP synthesis or hydrolysis, utilization or accumulation of energy are considered. Data on passive and active proton (H+) fluxes through the bacterial membranes are analyzed and their relationship with membrane H+ conductance (Gm(H+)) and permeability for H+ (P(H+)) is discussed. Methods for determination of bacterial membrane Gm(H+) are presented and some difficulties in obtaining and interpreting data are pointed out. Different ways and mechanisms of passive and active H+ fluxes, including a role of membrane lipids in H+ transfer, importance of phase transitions in lipid bilayers, operation of protonophores as well as H+ translocation via the F0 factor of the F0F1-ATPase, are discussed. Dependence of Gm(H+) for Escherichia coli, Enterococcus hirae, Streptococcus lactis and other bacteria on some external physico-chemical growth factors, particularly, on pH and oxidation reduction potential as well as influence of osmotic stress on Gm(H+) and H+ active fluxes through the bacterial membrane under fermentation have been shown. The relationship between Gm(H+), P(H+) and active H+ fluxes through a membrane is proposed, possible mechanisms of relationship between their alterations depending on pH and oxidation reduction potential are discussed. The results are important for understanding the structural and functional properties of bacterial membranes determining H+ cycles operation and mechanisms of H+ fluxes essential in adaptation of bacteria to altered environment conditions.
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PMID:[Proton cycles through membranes in bacteria: relationship between proton passive and active fluxes and their dependence on some external physico-chemical factors under fermentation]. 2548 47


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