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)

Nucleotide sequencing of the right end of the SalIj fragment of the highly virulent Malawi Lil20/1 strain of African swine fever virus (ASFV) has revealed three adjacent genes with similarity to: serine-threonine protein kinases; members of the putative helicase superfamily SF2; and the vaccinia virus 56 kDa abortive late protein. All three genes are transcribed to the left with respect to the orientation of the ASFV genome. Gene L19IL predicts a protein similar to serine-threonine protein kinases including vaccinia virus gene B1R. Gene L19KL predicts a protein that is likely to be a nucleic acid-dependent ATPase, as it has similarity to both the poxvirus 70 kDa early transcription factor subunit and the poxvirus nucleoside triphosphatase I gene. Gene L19LL has extensive similarity to the vaccinia virus 56 kDa abortive late protein.
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PMID:Three adjacent genes of African swine fever virus with similarity to essential poxvirus genes. 839 1

Two normal, two tumour, one transformed fibroblast cell line established from Ataxia telangiectasia (AT) patients and one corrected AT hybrid were characterised with regard to alpha, beta, SF2, and D values. Survival of 60Co gamma-irradiated tumour and transformed cells was markedly reduced when the Na+, K+-ATPase inhibitor ouabain was present 1 hr before and 3 hr post irradiation. Under these conditions, the radiosensitivity in normal cells remained virtually unchanged. Suppression of repair was found to play a role in the ouabain-induced inhibition of the cell survival. In A549 lung carcinoma cells, addition of 10(-8) M ouabain decreases the sublethal damage recovery ratio from 56.5 to 13.3. The same drug concentration decreases the recovery ratio in L132 epithelial cells only from 5.1 to 4.9. The fast repair component, as measured over the first 1.5 hr after irradiation, decreases from 1.83 to 0.36 hr(-1) in A549 cells and from 0.35 to 0.16 hr(-1) in HeLa cells. For 2 Gy fractions, the presence of 10(-8) M ouabain 1 hr before irradiation and 3 hr after irradiation induces dose enhancement ratios of 1.15-1.5. A more pronounced effect on cell inactivation may be expected from multiple fractions. The concentrations required to downregulate sublethal damage repair fall within the range where cardiac glycosides are used clinically. Application of these drugs in radiotherapy thus seems feasible.
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PMID:Na+, K+-ATPase inhibitor, ouabain accentuates irradiation damage in human tumour cell lines. 965 9

The human coronavirus 229E replicase gene encodes a protein, p66HEL, that contains a putative zinc finger structure linked to a putative superfamily (SF) 1 helicase. A histidine-tagged form of this protein, HEL, was expressed using baculovirus vectors in insect cells. The purified recombinant protein had in vitro ATPase activity that was strongly stimulated by poly(U), poly(dT), poly(C), and poly(dA), but not by poly(G). The recombinant protein also had both RNA and DNA duplex-unwinding activities with 5'-to-3' polarity. The DNA helicase activity of the enzyme preferentially unwound 5'-oligopyrimidine-tailed, partial-duplex substrates and required a tail length of at least 10 nucleotides for effective unwinding. The combined data suggest that the coronaviral SF1 helicase functionally differs from the previously characterized RNA virus SF2 helicases.
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PMID:The human coronavirus 229E superfamily 1 helicase has RNA and DNA duplex-unwinding activities with 5'-to-3' polarity. 1091

The arterivirus equine arteritis virus nonstructural protein 10 (nsp10) has previously been predicted to contain a Zn finger structure linked to a superfamily 1 (SF1) helicase domain. A recombinant form of nsp10, MBP-nsp10, was produced in Escherichia coli as a fusion protein with the maltose-binding protein. The protein was partially purified by affinity chromatography and shown to have ATPase activity that was strongly stimulated by poly(dT), poly(U), and poly(dA) but not by poly(G). The protein also had both RNA and DNA duplex-unwinding activities that required the presence of 5' single-stranded regions on the partial-duplex substrates, indicating a 5'-to-3' polarity in the unwinding reaction. Results of this study suggest a close functional relationship between the arterivirus nsp10 and the coronavirus helicase, for which NTPase and duplex-unwinding activities were recently demonstrated. In a number of biochemical properties, both arterivirus and coronavirus SF1 helicases differ significantly from the previously characterized RNA virus SF1 and SF2 enzymes. Thus, the combined data strongly support the idea that nidovirus helicases may represent a separate group of RNA virus-encoded helicases with distinct properties.
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PMID:Biochemical characterization of the equine arteritis virus helicase suggests a close functional relationship between arterivirus and coronavirus helicases. 1100 Feb 30

SF1 and SF2 helicases have structurally conserved cores containing seven to eight distinctive motifs and variable amino- and carboxyl-terminal flanking sequences. We have discovered a motif upstream of motif I that is unique to and characteristic of the DEAD box family of RNA helicases. It consists of a 9 amino acid sequence containing an invariant glutamine. A conserved phenylalanine occurs 17 aa further upstream. Sequence alignments, site-specific mutagenesis, and ATPase assays show that this motif and the upstream phenylalanine are highly conserved, that they are essential for viability in the yeast Saccharomyces cerevisiae, and that they control ATP binding and hydrolysis in the yeast translation-initiation factor eIF4A. These results are consistent with computer studies of the solved crystal structures.
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PMID:The Q motif: a newly identified motif in DEAD box helicases may regulate ATP binding and hydrolysis. 1253 27

Yeast (Saccharomyces cerevisiae) SWI/SNF is a prototype for a large family of ATP-dependent chromatin-remodeling enzymes that facilitate numerous DNA-mediated processes. Swi2/Snf2 is the catalytic subunit of SWI/SNF, and it is the founding member of a novel subfamily of the SF2 superfamily of DNA helicase/ATPases. Here we present a functional analysis of the diagnostic set of helicase/ATPase sequence motifs found within all Swi2p/Snf2p family members. Whereas many of these motifs play key roles in ATP binding and/or hydrolysis, we identify residues within conserved motif V that are specifically required to couple ATP hydrolysis to chromatin-remodeling activity. Interestingly, motif V of the human Swi2p/Snf2p homolog, Brg1p, has been shown to be a possible hot spot for mutational alterations associated with cancers.
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PMID:A conserved Swi2/Snf2 ATPase motif couples ATP hydrolysis to chromatin remodeling. 1598 5

Coupling of transcription and DNA repair in bacteria is mediated by transcription-repair coupling factor (TRCF, the product of the mfd gene), which removes transcription elongation complexes stalled at DNA lesions and recruits the nucleotide excision repair machinery to the site. Here we describe the 3.2 A-resolution X-ray crystal structure of Escherichia coli TRCF. The structure consists of a compact arrangement of eight domains, including a translocation module similar to the SF2 ATPase RecG, and a region of structural similarity to UvrB. Biochemical and genetic experiments establish that another domain with structural similarity to the Tudor-like domain of the transcription elongation factor NusG plays a critical role in TRCF/RNA polymerase interactions. Comparison with the translocation module of RecG as well as other structural features indicate that TRCF function involves large-scale conformational changes. These data, along with a structural model for the interaction of TRCF with the transcription elongation complex, provide mechanistic insights into TRCF function.
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PMID:Structural basis for bacterial transcription-coupled DNA repair. 1646 98

Reverse gyrase is a unique type IA topoisomerase that is able to introduce positive supercoils into DNA in an ATP-dependent process. ATP is bound to the helicase-like domain of the enzyme that contains most of the conserved motifs found in helicases of the SF1 and SF2 superfamilies. In this paper, we have investigated the role of the conserved helicase motifs I, II, V, VI, and Q by generating mutants of the Thermotoga maritima reverse gyrase. We show that mutations in motifs I, II, V, and VI completely eliminate the supercoiling activity of reverse gyrase and that a mutation in the Q motif significantly reduces this activity. Further analysis revealed that for most mutants, the DNA binding and cleavage properties are not significantly changed compared with the wild type enzyme, whereas their ATPase activity is impaired. These results clearly show that the helicase motifs are tightly involved in the coupling of ATP hydrolysis to the topoisomerase activity. The zinc finger motif located at the N-terminal end of reverse gyrases was also mutated. Our results indicate that this motif plays an important role in DNA binding.
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PMID:Mutational analysis of the helicase-like domain of Thermotoga maritima reverse gyrase. 1861 30

XPB, the largest subunit of the eukaryotic transcription factor TFIIH, is essential for both initiation of transcription by RNA polymerase II and nucleotide excision repair (NER). XPB belongs to the SF2 superfamily of monomeric helicases. XPB helicase is thought to have evolved in eukaryotes; however, a gene highly homologous to human XPB can be found in a number of bacteria. This report is the first biochemical characterization of XPB homologues from bacteria, specifically those from Mycobacterium tuberculosis and Kineococcus radiotolerans. Similarly to eukaryotic XPB, bacterial XPB are ATP-dependent 3' --> 5' DNA helicases. The ATPase activity of these XPB helicases is DNA-dependent, requiring a minimum of 4-nucleotide long single-stranded DNA (ssDNA). The maximum rates of ATP hydrolysis are about 10 and 50 molecules per minute by one XPB monomer on a 21-nucleotide ssDNA oligomer and on 5-kb long circular ssDNA, respectively. The ATP hydrolysis by the bacterial XPBs is coupled to their translocation along single-stranded DNA. The hydrolytic activity is strongly dependent on both the nature of a nucleotide triphosphate and that of a divalent metal. The inefficient ATP hydrolysis by bacterial XPB is consistent with nonprocessive functions of its eukaryotic homologue in locally remodeling DNA during transcription initiation and NER.
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PMID:DNA-dependent ATPase activity of bacterial XPB helicases. 1919 47

Many double-stranded DNA viruses employ ATP-driven motors to translocate their genomes into small, preformed viral capsids against large forces resisting confinement. Here, we show via direct single-molecule measurements that a mutation T194M downstream of the Walker B motif in the phage lambda gpA packaging motor causes an 8-fold reduction in translocation velocity without substantially changing processivity or force dependence, whereas the mutation G212S in the putative C (coupling) motif causes a 3-fold reduction in velocity and a 6-fold reduction in processivity. Meanwhile a T194M pseudorevertant (T194V) showed a near restoration of the wild-type dynamics. Structural comparisons and modeling show that these mutations are in a loop-helix-loop region that positions the key residues of the catalytic motifs, Walker B and C, in the ATPase center and is structurally homologous with analogous regions in chromosome transporters and SF2 RNA helicases. Together with recently published studies of SpoIIIE chromosome transporter and Ded1 RNA helicase mutants, these findings suggest the presence of a structurally conserved region that may be a part of the mechanism that determines motor velocity and processivity in several different types of nucleic acid translocases.
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PMID:Mutations altering a structurally conserved loop-helix-loop region of a viral packaging motor change DNA translocation velocity and processivity. 2052 95


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