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)

In the inbred Dahl salt-sensitive rat (SS/Jr strain), it has been proposed that a T for A transversion in the DNA sequence encoding amino acid 276 in the alpha 1 subunit isoform of Na+,K(+)-ATPase may impair ion transport and contribute to the pathogenesis of hypertension. This hypothesis is of major scientific interest because it represents the first attempt to explain the pathogenesis of salt-sensitive hypertension on the basis of a specifically defined mutation at the DNA level. We devised a polymerase chain reaction technique to screen the genomic DNA of multiple SS/Jr rats for the T for A transversion reported in the complementary DNA (cDNA) encoding the alpha 1 subunit of Na+,K(+)-ATPase. When eight Dahl SS/Jr rats from Harlan Sprague Dawley Inc. were tested with the polymerase chain reaction technique, we found no evidence of this mutation in the Na+,K(+)-ATPase gene. Direct sequence analysis of the gene in three SS/Jr rats also did not show the T for A transversion. These results 1) strongly suggest that commercially available Dahl SS/Jr rats do not carry a T for A transversion in the genomic DNA sequence encoding amino acid 276 in the alpha 1 subunit isoform of Na+,K(+)-ATPase and 2) raise the possibility that the previous finding of a mutation in the cDNA of the SS/Jr rat may have been due to a reverse transcriptase error during cDNA synthesis.
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PMID:Sequence analysis of the alpha 1 Na+,K(+)-ATPase gene in the Dahl salt-sensitive rat. 131 80

9-(2-Phosphonylmethoxyethyl)adenine (PMEA) is a potent and selective inhibitor of retrovirus (i.e., human immunodeficiency virus) replication in vitro and in vivo. Uptake of PMEA by human MT-4 cells and subsequent conversion to the mono- and diphosphorylated metabolites (PMEAp and PMEApp) are dose-dependent and occur proportionally with the initial extracellular PMEA concentrations. Adenylate kinase is unable to phosphorylate PMEA. However, 5-phosphoribosyl-1-pyrophosphate synthetase directly converts PMEA to PMEApp with a Km of 1.47 mM and a Vmax that is 150-fold lower than the Vmax for AMP. ATPase, 5'-phosphodiesterase, and nucleoside diphosphate kinase are able to dephosphorylate PMEApp to PMEAp, albeit to a much lower extent than the dephosphorylation of ATP. PMEApp has a relatively long intracellular half-life (16-18 hr) and has a much higher affinity for the human immunodeficiency virus-specified reverse transcriptase than for the cellular DNA polymerase alpha (Ki/Km: 0.01 and 0.60, respectively). PMEApp is at least as potent an inhibitor of human immunodeficiency virus reverse transcriptase as 2',3'-dideoxyadenosine 5'-triphosphate. Being an alternative substrate to dATP, PMEApp acts as a potent DNA chain terminator, and this may explain its anti-retrovirus activity.
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PMID:Intracellular metabolism and mechanism of anti-retrovirus action of 9-(2-phosphonylmethoxyethyl)adenine, a potent anti-human immunodeficiency virus compound. 170 39

Chemical modification of unpaired bases is demonstrated in this study to be a reliable method for determining the conformation of nucleotides in mRNA. The modified nucleotides are identified by primer extension using reverse transcriptase. We have used this procedure to compare the structure of limited regions of SV40 T-antigen mRNA in solution, in nonpolysome-bound cytoplasmic messenger ribonucleoprotein particles, and in nuclear ribonucleoprotein complexes. The results indicate that SV40 T-antigen mRNA adopts a specific structure both in solution and when complexed with cellular proteins. The structures adopted by the mRNA in solution and in native cellular protein particles are very similar.
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PMID:Chemical modification as a tool for analysis of messenger RNA secondary structure in ribonucleoprotein particles. 245 87

RNA-dependent DNA polymerase activity of avian myeloblastosis virions as measured by the incorporation of [3H]TTP into trichloroacetic acid-precipitable material was very low. This apparent low polymerase activity was observed with virions isolated either from leukemic chicken plasma or from the supernatant of cultured leukemic myeloblasts. The inhibition of reverse transcriptase activity was caused by nucleoside triphosphatase present in avian myeloblastosis virions and could be reversed by ADP.
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PMID:Inhibition of virion-associated reverse transcription by nucleoside triphosphatase in avian myeloblastosis virus. 615 6

The Mn2+-dependent endonuclease activity associated with the avian myeloblastosis virus RNA-directed DNA polymerase has been shown to be activated by ATP in the presence of Mg2+. In the presence of Mn2+ the endonucleolytic activity was stimulated about 3-fold by the addition of ATP. The earlier identified Mr = 40,000 Friend murine leukemia virus (F-MuLV)-associated endonuclease which functions in the presence of both Mg2+ and Mn2+ has also been shown to be similarly stimulated by ATP. For both endonuclease activities stimulation was only observed at ATP concentrations above 0.5 mM, and it did not increase upon elevating the ATP concentration above 2.5 mM. ADP and dATP also stimulated both activities, although not to the same extent as ATP. GTP had no apparent effect and AMP seemed to inhibit both activities. The effect ATP analogs had on the F-MuLV associated endonuclease activity could suggest that the endonuclease reaction in the presence of ATP might involve the cleavage of beta-gamma phosphate bonds in ATP. Neither adenyl-5'-yl imidodiphosphate nor (beta, gamma-methylene)adenosine 5'-triphosphate stimulated the activity, whereas significant stimulation was observed in the presence of (alpha, beta-methylene)adenosine 5'-triphosphate. Although no ATPase activity could be detected in the purified F-MuLV endonuclease preparation, the data do not exclude the possibility that ATP may be cleaved in amounts which are equivalent to the number of nicks introduced into DNA by the virus-associated endonuclease. In the presence of ATP and Mg2+ the F-MuLV-associated endonuclease nicked both supercoiled and linear DNA duplexes extensively, although the former was nicked more readily than the latter. Single-stranded DNA functioned poorly as a substrate. The nicks introduced by the enzyme contained a 5'-phosphoryl terminus and a 3'-hydroxyl group.
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PMID:Effect of ATP on the Friend Murine leukemia virus-associated endonuclease activity and the endonuclease activity of the avian myeloblastosis virus RNA-directed DNA polymerase. 616 71

The p30 antigen from Rauscher leukemia virus (R-MuLV) was separated into two fractions by chromatography on either phosphocellulose or DEAE-cellulose. The p30-I and p30-II were indistinguishable immunologically or by isoelectrofocusing and gel electrophoresis. An ATPase activity was tightly associated with p30-II that could not be separated by ion-exchange chromatography, isoelectrofocusing, or glycerol velocity gradient sedimentation. The ATPase hydrolyzed the gamma phosphate from only ATP or dATP. Immunoglobulin directed against R-MuLV p30 completely inhibited the p30-II associated ATPase. Glycerol velocity gradient analysis showed that p30-I sedimented as a 30-kDa species while the p30-II and its associated ATPase sedimented as a 60-kDa species. The p30-II was converted entirely to a 30-kDa form by treatment with 0.2% (w/v) lithium dodecyl sulfate, suggesting that it represented a complexed species of p30. Finally, p30-II was found to stimulate the activity of R-MuLV reverse transcriptase, but p30-I had no effect on the activity of the enzyme. These results suggested the existence of at least two different forms of p30 in R-MuLV.
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PMID:Characterization of a p30 fraction from Rauscher leukemia virus which has an associated ATPase activity. 620 91

During the course of serial passage of 50 human xenografts in the athymic mouse over a period of 5 years we have observed two cases of induction of sarcomas in the murine stromal tissue associated with the human xenografts. Both times the growth of the murine sarcomas overtook that of the human xenograft. This change was monitored by analysis of the lactate dehydrogenase isozyme profile and histology of each passage of the human xenografts in the athymic mice. The two murine sarcomas were subsequently established in tissue culture. The sarcoma cell lines were found to be malignant by morphological and growth characteristics and were tumorigenic. They contained large amounts of murine leukemia virus when assayed for reverse transcriptase activity by infection of mouse SC-1 cells and BALB/c and NIH Swiss fibroblasts with filtered supernates, and some type C virus particles were observed by electron microscopy in tumor tissues. However, we were unable to demonstrate the presence of murine sarcoma virus by in vitro transformation of fibroblasts or sarcoma formation in vivo will cell free filtrates. Preliminary biochemical data indicate that the sarcomas are extremely high in plasma membrane ATP phosphohydrolase.
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PMID:Induction of sarcomas in athymic mice. 628 53

It is now widely accepted that proton secretion by the collecting duct is mediated, in part, by an H(+)-K(+)-adenosinetriphosphatase (H(+)-K(+)-ATPase). Controversy persists regarding which H(+)-K(+)-ATPase isoform is expressed in kidney. Several laboratories have reported preliminarily the amplification from kidney of stomach and/or colon-identical products using gastric or colonic-specific primers in the polymerase chain reaction (PCR). We have developed highly specific probes for the catalytic subunit using reverse transcriptase-PCR with gastric- or colonic-specific primers. The resulting cDNAs were verified by sequencing and were then used in Northern analysis of whole kidney total RNA obtained from one of the following three groups of rats: 1) controls, 2) chronic hypokalemia, or 3) chronic metabolic acidosis. Probes for both the colonic and gastric alpha-subunit H(+)-K(+)-ATPase isoforms hybridized to whole kidney total RNA derived from potassium-replete control rats. A marked elevation of colonic mRNA abundance, but not gastric message, was observed in response to chronic hypokalemia induced by dietary potassium deprivation. Elevation of either gastric or colonic mRNA was not observed with chronic metabolic acidosis. Under the conditions of the present study, it appears that the mRNA encoding the colonic alpha-isoform of the H(+)-K(+)-ATPase in kidney is upregulated by chronic hypokalemia but not by chronic metabolic acidosis. The observation that the gastric H(+)-K(+)-ATPase alpha-isoform does not appear to be regulated in either condition suggests that this isoform is expressed constitutively in kidney.
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PMID:Regulation of H(+)-K(+)-ATPase expression in kidney. 748 34

In addition to the gastric isoform of H-K-ATPase, the colonic isoform is also expressed in the kidney, but its intrarenal localization and exact function are not known. The goal of this study was to determine whether the colonic H-K-ATPase is expressed in the rabbit cortical collecting duct (CCD) and whether it is regulated by changes in acid/base balance. With quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) with RNA isolated from immunodissected rabbit CCD cells and degenerate oligonucleotide primers, a PCR product of the predicted size (approximately 430 bp) was amplified. The amplified DNA was further characterized by nested PCR and sequencing. Direct sequencing of the 434-bp PCR product revealed 83% identity at the nucleotide level and an 80.4% identity at the deduced amino acid level to the rat colonic H-K-ATPase. With the same primers and cDNA originating from rabbit distal colon, a DNA fragment with a size and nucleotide sequence identical to that originating from CCD cells was amplified. Furthermore, using PCR screening, we isolated and sequenced a 1.5-kb cDNA clone from a rabbit CCD library. The predicted amino acid sequence of the protein encoded by this cDNA is 85 and 82% identical to the corresponding regions of the guinea pig and rat colonic H-K-ATPase, respectively, and 70% identical to the H-K-ATPase recently cloned from Bufo marinus, whereas it shows only 45 and 42% homology to the rat Na-K-ATPase alpha 1-subunit and the rat gastric H-K-ATPase, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Expression of colonic H-K-ATPase mRNA in cortical collecting duct: regulation by acid/base balance. 748 41

Using 3D searching techniques based on algorithms derived from graph theory, we have established two previously unreported structural similarities involving the ribonuclease H (RNase H) domain of HIV-1 reverse transcriptase (RT). First, we report that there is a strong similarity between the 3D folds of the RNase H domain of RT and the 'ATPase folds' of hexokinase, the 70 kDa heat-shock cognate protein and actin. Like RNase H, these enzymes are involved in nucleotide binding and metal ion-catalysed cleavage of a phosphodiester bond. Similarities of the folding motif and the position of the metal-binding site in these enzymes suggest possible functional analogies and evolutionary relationships with RNase H. Second, we find there is a strong resemblance between the folds of the RNase H domain and of the p66 and p51 'connection' domains of RT. It is possible that this striking similarity within the RT structure indicates a possible ancestral gene doubling event. The similarity may also indicate that the connection domains possess functional roles in addition to those previously suggested, and they may therefore represent a further target for the design of therapeutic agents.
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PMID:Three-dimensional structural resemblance between the ribonuclease H and connection domains of HIV reverse transcriptase and the ATPase fold revealed using graph theoretical techniques. 768 87


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