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)

We have cloned a cDNA encoding the human 150 kDa oxygen-regulated protein (ORP150) from hypoxia-treated astrocytoma U373 cDNA library. The deduced amino acid sequence of 999 residues contains a signal peptide and an ER retention-like signal at the N- and C-termini, respectively. It has a striking sequence similarity (91% identity) with Chinese hamster 170 kDa glucose-regulated protein (GRP170). The N-terminal half of ORP150 exhibits significant similarity to the ATPase domain of HSP70 family proteins with well-conserved ATP binding motifs. Northern blot analysis revealed that induction of ORP150 in U373 cells was not limited to hypoxia but also observed by 2-deoxyglucose or tunicamycin treatment. Furthermore, tissue specificity of expression of ORP150 was quite similar to that of GRP78. These findings suggest that ORP150 participates in quality control of proteins in the ER in response to diverse environmental stresses.
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PMID:Cloning and expression of cDNA encoding the human 150 kDa oxygen-regulated protein, ORP150. 902 69

The positive-strand RNA genome of beet yellows closterovirus (BYV) encodes a 65 kDa protein (p65) related to the HSP70 family of cell chaperones. The full-sized BYV p65, and N- and C-terminal fragments, with (His)6 tails, were overexpressed in bacteria and purified by metal-chelate chromatography. Using a polyclonal antiserum raised against the C-terminal fragment of p65, evidence was obtained for expression of the viral protein in planta. Purified recombinant p65 and its N-terminal 40 kDa fragment exhibited Mg2+-dependent ATPase activity in vitro. However, unlike its cellular HSP70 homologues, p65 was unable to bind to denatured protein and its ATPase activity was not stimulated by synthetic peptides which are known to stimulate HSP70 ATPases. Hence, the BYV p65, although being a chaperone-type ATPase, may have a distinct substrate specificity and function in BYV-infected cells.
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PMID:The beet yellows closterovirus p65 homologue of HSP70 chaperones has ATPase activity associated with its conserved N-terminal domain but does not interact with unfolded protein chains. 904 1

We have previously shown that the molecular chaperone HSC70 self-associates in solution into dimers, trimers, and probably high order oligomers, according to a slow temperature- and concentration-dependent equilibrium that is shifted toward the monomer upon binding of ATP peptides or unfolded proteins. To determine the structural basis of HSC70 self-association, the oligomerization properties of the isolated amino- and carboxyl-terminal domains of this protein have been analyzed by gel electrophoresis, size exclusion chromatography, and analytical ultracentrifugation. Whereas the amino-terminal ATPase domain (residues 1-384) was found to be monomeric in solution even at high concentrations, the carboxyl-terminal peptide binding domain (residues 385-646) exists as a slow temperature- and concentration-dependent equilibrium involving monomers, dimers, and trimers. The association equilibrium constant obtained for this domain alone is on the order of 10(5) M-1, very close to that determined previously for the entire protein, suggesting that self-association of HSC70 is determined solely by its carboxyl-terminal domain. Furthermore, oligomerization of the isolated carboxyl-terminal peptide binding domain is, like that of the entire protein, reversed by peptide binding, indicating that self-association of the protein may be mediated by the peptide binding site and, as such, should play a role in the regulation of HSC70 chaperone function. A general model for self-association of HSP70 is proposed in which the protein is in equilibrium between two states differing by the conformation of their carboxyl-terminal domain and their self-association properties.
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PMID:The COOH-terminal peptide binding domain is essential for self-association of the molecular chaperone HSC70. 907 9

The crystal structure of the adenine nucleotide exchange factor GrpE in complex with the adenosine triphosphatase (ATPase) domain of Escherichia coli DnaK [heat shock protein 70 (Hsp70)] was determined at 2.8 angstrom resolution. A dimer of GrpE binds asymmetrically to a single molecule of DnaK. The structure of the nucleotide-free ATPase domain in complex with GrpE resembles closely that of the nucleotide-bound mammalian Hsp70 homolog, except for an outward rotation of one of the subdomains of the protein. This conformational change is not consistent with tight nucleotide binding. Two long alpha helices extend away from the GrpE dimer and suggest a role for GrpE in peptide release from DnaK.
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PMID:Crystal structure of the nucleotide exchange factor GrpE bound to the ATPase domain of the molecular chaperone DnaK. 910 5

Rats were subjected to transient cerebral ischemia by four-vessel occlusion of 30 min duration, followed by 2, 4, 8 or 24 h of recovery. Total RNA was isolated from the cerebral cortex and hippocampus, and reverse transcribed into cDNA. Hsp40 mRNA levels of samples were evaluated by quantitative PCR. Transient cerebral ischemia caused a marked increase in hsp40 mRNA levels to about 250% and 500% of control in the cortex and hippocampus respectively. Since hsp40 exerts a critical regulatory function in the HSC70/HSP70 ATPase cycle, an ischemia-induced rise of hsp40 mRNA levels could mark the onset of the recovery process after transient ischemia. On the other hand, the inhibitory action of hsp40 on P58 (a protein that activates protein synthesis by blocking the interferon-induced double-stranded RNA-activated protein kinase PKR) implies that the rise in hsp40 expression may equally well contribute to the post-ischemic suppression of protein synthesis.
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PMID:Effects of transient cerebral ischemia on hsp40 mRNA levels in rat brain. 958 51

The frequency of oxidative base damage, such as 8-hydroxyguanine (8-OH-Gua), was determined at the nucleotide level of resolution using the ligation-mediated PCR technique. Administration of a renal carcinogen, ferric nitrilotriacetate (Fe-NTA), is known to induce oxidative stress and subsequent formation of 8-OH-Gua in the rat kidney. Whole genomic DNA was isolated from the rat kidney after or without Fe-NTA treatment and then cleaved with hot piperidine. In order to assess the frequency of 8-OH-Gua formation, we chose three genes, the tumor suppressor gene p53, the heat shock protein 70 (HSP70-1) gene and the Na,K-ATPase alpha1 subunit gene. No alteration in the cleavage profile was observed in the p53 and HSP70 genes after Fe-NTA treatment. In the case of the p53 gene, a low incidence of point mutations has been observed in this carcinogenesis system. On the other hand, time-dependent alterations, corresponding to the time course of overall 8-OH-Gua formation and repair, were detected in the promoter region of the Na,K-ATPase alpha1 subunit gene. GpG and GpGpG in specific regions seem to be hotspots for the formation of 8-OH-Gua. These results were confirmed by formamidopyrimidine-DNA glycosylase-dependent DNA cleavage patterns. Thus, oxidative base damage, such as 8-OH-Gua, was not distributed uniformly along the whole genome, but seemed to be restricted to particular genes and regions.
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PMID:Analysis of 8-hydroxyguanine in rat kidney genomic DNA after administration of a renal carcinogen, ferric nitrilotriacetate. 1033 1

Heat shock proteins (HSP) are conserved proteins, many of which share the ability for indiscriminate peptide binding and ATPase-coupled peptide release. In this paper, we show that heat shock cognate protein (HSC)73, a constitutively expressed member of the HSP70 family, could be a candidate for chaperone activity within the MHC class II presentation pathway. HSC73 expression in macrophages was shown to overlap with expression of MHC class II; overexpression of HSC73 in stable transfectants of a macrophage line markedly enhanced their presentation of exogenous Ag without affecting presentation of processing independent peptide. Ag from an exogenous source was demonstrated to associate with HSC73 in macrophages, and this association was sensitive to ATP treatment and inhibited by deoxyspergualin, an immunosuppressive agent that has previously been shown to bind specifically to HSC73. Furthermore, deoxyspergualin reduced Ag presentation by macrophages in relation to the amount of HSC73 expressed in these cells. The data are consistent with a potential role for HSC73 in binding and protecting peptides from extensive degradation and/or facilitating the kinetics of peptide transfer to MHC class II molecules.
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PMID:The HSC73 molecular chaperone: involvement in MHC class II antigen presentation. 1043 29

BiP, a resident endoplasmic reticulum member of the HSP70 family of molecular chaperones, associates transiently with a wide variety of newly synthesized exocytotic proteins. In addition to immunoglobulin heavy and light chains, the first natural substrates identified for BiP, a number of viral polypeptides including the human immunodeficiency virus type 1 envelope glycoprotein gp160 interact with BiP during their passage through the endoplasmic reticulum. We have used a computer algorithm developed to predict BiP-binding sites within protein primary sequences to identify sites within gp160 that might mediate its association with BiP. Analysis of the ability of 22 synthetic heptapeptides corresponding to predicted binding sites to stimulate the ATPase activity of BiP or to compete with an unfolded polypeptide for binding to BiP indicated that about half of them are indeed recognized by the chaperone. All of the confirmed binding sites are localized within conserved regions of gp160, suggesting a conserved role for BiP in the folding of gp160. Information on the characteristics of confirmed BiP-binding peptides gained in this and previous studies has been utilized to improve the predictive power of the BiP Score algorithm and to investigate the differences in peptide binding specificities of HSP70 family members.
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PMID:BiP-binding sequences in HIV gp160. Implications for the binding specificity of bip. 1051 65

Preparations of Escherichia coli DnaK from our lab as well as preparations of DnaK and other HSP70 proteins from several major labs in the field produce a stoichiometric initial burst of [alpha-(32)P]ADP when incubated with [alpha-(32)P]ATP and contain an ADP kinase activity. We determined that the initial burst activity results from the transfer of gamma-phosphate from the radiolabeled substrate [alpha-(32)P]ATP to unlabeled ADP bound by the DnaK and is the same activity that results in ADP phosphorylation. The purification of DnaK from E. coli cells that carry a disrupted ndk gene, ndk::km, results in preparations with greatly reduced ADP kinase activities compared with preparations of DnaK purified from ndk(+) cells. The reduction in the amount of ADP kinase activity in preparations of DnaK purified from ndk::km cells shows that nucleoside-diphosphate kinase (NDP kinase) is responsible for most of the ADP kinase activity present in DnaK preparations isolated from ndk(+) cells. The remaining ADP kinase activity in preparations from ndk::km cells, which varies between preparations, is also a property of NDP kinase, which is most likely expressed because of a low frequency reversion of the disrupted ndk gene. A weak, but measurable physical interaction exists between DnaK and NDP kinase and may be at least partially responsible for the co-purification of NDP kinase with DnaK. The presence of contaminating NDP kinase can explain the range of k(cat) values reported for the ATPase activity of DnaK as well as recent reports of initial burst kinetics by DnaK (Banecki, B., and Zylicz, M. (1996) J. Biol. Chem. 271, 6137-6143) and an ADP-ATP exchange activity of DnaK (Hiromura, M., Yano, M., Mori, H., Inoue, M., and Kido, H. (1998) J. Biol. Chem. 273, 5435-5438).
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PMID:Inferences concerning the ATPase properties of DnaK and other HSP70s are affected by the ADP kinase activity of copurifying nucleoside-diphosphate kinase. 1059 71

Plant closteroviruses encode a homolog of the HSP70 (heat shock protein, 70 kDa) family of cellular proteins. To facilitate studies of the function of HSP70 homolog (HSP70h) in viral infection, the beet yellows closterovirus (BYV) was modified to express green fluorescent protein. This tagged virus was competent in cell-to-cell movement, producing multicellular infection foci similar to those formed by the wild-type BYV. Inactivation of the HSP70h gene by replacement of the start codon or by deletion of 493 codons resulted in complete arrest of BYV translocation from cell to cell. Identical movement-deficient phenotypes were observed in BYV variants possessing HSP70h that lacked the computer-predicted ATPase domain or the C-terminal domain, or that harbored point mutations in the putative catalytic site of the ATPase. These results demonstrate that the virus-specific member of the HSP70 family of molecular chaperones functions in intercellular translocation and represents an additional type of a plant viral-movement protein.
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PMID:HSP70 homolog functions in cell-to-cell movement of a plant virus. 1061 Dec 88


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