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:2.7.7.48 (transcriptase)
9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report the first sequence analysis of the entire complement of M-class genome segments of an avian reovirus (ARV). We analyzed the M1, M2 and M3 genome segment sequences, and sequences of the corresponding muA, muB and muNS proteins, of two virus strains, ARV138 and ARV176. The ARV M1 genes were 2,283 nucleotides in length and predicted to encode muA proteins of 732 residues. Alignment of the homologous mammalian reovirus (MRV) mu2 and ARV muA proteins revealed a relatively low overall amino acid identity ( approximately 30%), although several highly conserved regions were identified that may contribute to conserved structural and/or functional properties of this minor core protein (i.e. the MRV mu2 protein is an NTPase and a putative RNA-dependent RNA polymerase cofactor). The ARV M2 genes were 2158 nucleotides in length, encoding predicted muB major outer capsid proteins of 676 amino acids, more than 30 amino acids shorter than the homologous MRV mu1 proteins. In spite of the difference in size, the ARV/MRV muB/mu1 proteins were more conserved than any of the homologous proteins encoded by other M- or S-class genome segments, exhibiting percent amino acid identities of approximately 45%. The conserved regions included the residues involved in the maturation- and entry- specific proteolytic cleavages that occur in the MRV mu1 protein. Notably missing was a region recently implicated in MRV mu1 stabilization and in forming "hub and spokes" complexes in the MRV outer capsid. The ARV M3 genes were 1996 nucleotides in length and predicted to encode a muNS non-structural protein of 635 amino acids, significantly shorter than the homologous MRV muNS protein, which is attributed to several substantial deletions in the aligned ARV muNS proteins. Alignments of the ARV and MRV muNS proteins revealed a low overall amino acid identity ( approximately 25%), although several regions were relatively conserved.
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PMID:Sequences of avian reovirus M1, M2 and M3 genes and predicted structure/function of the encoded mu proteins. 1629 81

There are a number of antivirals as well as antiviral strategies that could be envisaged to prevent or treat severe acute respiratory syndrome (SARS) (or similar) coronavirus (CoV) infections. Targets for the prophylactic or therapeutic interventions include interaction of the spike (S) glycoprotein (S1 domain) with the host cell receptor, fusion of the S2 domain with the host cell membrane, processing of the replicase polyproteins by the virus-encoded proteases (3C-like cysteine protease [3CLpro] and papain-like cysteine protease) and other virus-encoded enzymes such as the NTPase/helicase and RNA-dependent RNA polymerase. Human monoclonal antibody blocking S1 may play an important role in the immunoprophylaxis of SARS. Fusion inhibitors reminiscent of enfuvirtide in the case of HIV may also be developed for SARS-CoV. Various peptidomimetic and nonpeptidic inhibitors of 3CLpro have been described, the best ones inhibiting SARS-CoV replication with a selectivity index greater than 1000. Human interferons, in particular alpha- and beta-interferon, as well as short interfering RNAs could further be pursued for the control of SARS. Various other compounds, often with an ill-defined mode of action but selectivity indexes up to 100, have been reported to exhibit in vitro activity against SARS-CoV: valinomycin, glycopeptide antibiotics, plant lectins, hesperetin, glycyrrhizin, aurintricarboxylic acid, chloroquine, niclosamide, nelfinavir and calpain inhibitors.
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PMID:Potential antivirals and antiviral strategies against SARS coronavirus infections. 1659 9

Dengue viruses (DENV) have 5'-capped RNA genomes of (+) polarity and encode a single polyprotein precursor that is processed into mature viral proteins. NS2B, NS3 and NS5 proteins catalyse/activate enzyme activities that are required for key processes in the virus life cycle. The heterodimeric NS2B/NS3 is a serine protease required for processing. Using a high-throughput protease assay, we screened a small molecule chemical library and identified -200 compounds having > or = 50% inhibition. Moreover, NS3 exhibits RNA-stimulated NTPase, RNA helicase and the 5'-RNA triphosphatase activities. The NTPase and the 5'-RTPase activities of NS3 are stimulated by interaction with NS5. Moreover, the conserved, positively charged motif in DENV-2 NS3, 184RKRK, is required for RNA binding and modulates the RNA-dependent enzyme activities of NS3. To study viral replication, a variety of methods are used such as the in vitro RNA-dependent RNA polymerase assays that utilize lysates from DENV-2-infected mosquito or mammalian cells or the purified NS5 along with exogenous short subgenomic viral RNAs or the replicative intracellular membrane-bound viral RNAs as templates. In addition, a cell-based DENV-2 replicon RNA encoding a luciferase reporter is also used to examine the role of cis-acting elements within the 3' UTR and the RKRK motif in viral replication.
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PMID:Multiple enzyme activities of flavivirus proteins. 1731 55

Four novel series of base modified ribonucleoside analogues were synthesized and evaluated as potential anti-HCV agents. For two compounds notable anti-HCV activity was observed The triphosphates of bicyclic pyrimidine ribonucleosides were studied as substrates/inhibitors of HCV RNA-dependent RNA polymerase (RdRp, NS5B protein) and RNA helicase/NTPase (NS3 protein).
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PMID:Base-modified ribonucleosides as potential anti-hepatitis C virus agents. 1877 32

Bacteriophage Phi6 contains three dsRNA genomic segments L, M, and S. The RNA is located inside a core particle composed of multiple copies of a major structural protein, an RNA-dependent RNA polymerase, a hexameric NTPase, and an auxiliary protein. The virion RNA polymerase in the core particle transcribes segments M and S in vitro. Yet early in infection, the transcription of L is highly active. Late in infection, transcription of L is low, and that of M and S is high. A host protein encoded by yajQ is responsible for the activation of L transcription. Knockout mutants of yajQ do not support the replication of Phi6, although they do support the replication of distantly related members of the Cystoviridae. Phi6 can mutate to independence of YajQ. This requires two mutations in the gene for the RNA-dependent RNA polymerase. YajQ acts indirectly on the polymerase by binding to P1, the major structural protein of the core. Previous studies have shown that the activity of the polymerase in the core is controlled by the conformation of the core particle structure.
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PMID:The role of host protein YajQ in the temporal control of transcription in bacteriophage Phi6. 1883 83

Bicyclic furano[2,3-d]pyrimidine ribonucleosides were synthesized by Pd(0)- and CuI-catalyzed coupling of 5-iodouridine with terminal alkynes. The treatment of the resulting nucleosides with ammonia or methylamine solution in aqueous alcohol resulted in pyrrolo- and N(7)-methylpyrrolo[2,3-d]pyrimidine nucleosides. 5'-O-Triphosphates of bicyclic nucleosides were obtained by the treatment of the nucleosides with POCl3 in the presence of a "proton sponge." The 5'-O-triphosphates are not substrates for HCV RNA-dependent RNA polymerase, but are effective substrates for HCV RNA helicase/NTPase and did not inhibit ATP hydrolysis. Only 3-(beta-D-ribofuranosyl)-6-decyl-2,3-dihydrofuro-[2,3-d]pyrimidin-2-one showed a moderate anti-HCV activity in the HCV replicon system and efficiently inhibited replication of bovine viral diarrhea virus (BVDV) in KCT-cells, other compounds being inactive. None of the compounds were cytotoxic within the tested range of concentrations.
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PMID:[New furano- and pyrrolo[2,3-d]pyrimidine nucleosides and their 5'-triphosphates: synthesis and biological properties]. 1906 Sep 41

Classical swine fever virus (CSFV) nonstructural protein 3 (NS3) is believed to possess three enzyme activities that are likely to be essential for virus replication: a serine protease located in the N-terminus and NTPase as well as helicase activities located in the C-terminus. In this report, we expressed NS3 helicase domain (NS3h) in E. coli and characterized its helicase activity. The NS3h helicase activity was dependent on the presence of NTP and divalent cations, with a preference for ATP and Mn(2+), and required the substrates possessing a 3' un-base-paired region on the RNA template strand. The NS3h helicase activity was proportional to increasing lengths of the 3' un-base-paired regions up to 16 nucleotides of the RNA substrates. We also investigated the modulation of NS3 NTPase/helicase activities by NS3 protease domain and NS5B, an RNA-dependent RNA polymerase (RdRp). Our data showed that the NS3 protease domain enhanced the helicase activity of NS3 but had no effect on its NTPase activity. For the truncated NS3 (helicase domain, NS3h), both NTPase and helicase activities were up-regulated by NS5B. However, for the full-length NS3 (NS3FL), the NTPase activity, but not the helicase activity, was stimulated by NS5B. Maltose-binding protein (MBP) pull-down as well as enzyme-linked immunosorbent assays confirmed the specific interaction between NS3 and NS5B.
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PMID:Characterization of classical swine fever virus (CSFV) nonstructural protein 3 (NS3) helicase activity and its modulation by CSFV RNA-dependent RNA polymerase. 1918 95

NS3 of pestiviruses contains a protease domain and a RNA helicase/NTPase domain. Contradictory results have been reported regarding NS3 in RNA synthesis. To investigate the effect of NS3 on classical swine fever virus (CSFV) NS5B RNA-dependent RNA polymerase activity (RdRp) activity and NS3-NS5B interaction, RdRp reactions, GST-pull-down assays and co-immunoprecipitation analyses containing NS5B and either of NS3 protein and the different truncated NS3 mutants were performed, respectively. We found that NS3 stimulated NS5B RdRp activity in a dose-dependent manner by binding to NS5 through a NS3 protease domain. Furthermore, mapping important regions of the NS3 protease domain was carried out by deletion mutagenesis, associated with RdRp reactions, GST-pull-down assays and co-immunoprecipitation analyses. Results showed that stimulation of CSFV NS5B RdRp activity was obtained by NS3 binding to NS5B through a 31-amino acid fragment at the N-terminal end of NS3 protease domain, which mediated a specific NS3-NS5B interaction.
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PMID:Classical swine fever virus NS3 enhances RNA-dependent RNA polymerase activity by binding to NS5B. 1995 25

Hepatitis E virus (HEV) is a causative agent of acute hepatitis, and it is the sole member of the genus Hepevirus in the family Hepeviridae. The open reading frame 1 (ORF1) protein of HEV encodes nonstructural polyprotein with putative domains for methyltransferase, cysteine protease, helicase and RNA-dependent RNA polymerase. It is not yet known whether ORF1 functions as a single protein with multiple domains or is processed to form separate functional units. On the basis of amino acid conserved motifs, HEV helicase has been grouped into helicase superfamily 1 (SF-1). In order to examine the RNA helicase activity of the NTPase/helicase domain of HEV, the region (amino acids 960 to 1204) was cloned and expressed as histidine-tagged protein in Escherichia coli (HEV Hel) and purified. HEV Hel exhibited NTPase and RNA unwinding activities. Enzyme hydrolyzed all rNTPs efficiently, dATP and dCTP with moderate efficiency, while it showed less hydrolysis of dGTP and dTTP. Enzyme showed unwinding of only RNA duplexes with 5' overhangs showing 5'-to-3' polarity. We also expressed and purified two HEV Hel mutants. Helicase mutant I, with substitution in the nucleotide-binding motif I (GKS to GAS), showed 30% ATPase activity. Helicase mutant II, with substitutions in the Mg(2+) binding motif II (DEAP to AAAP), showed 50% ATPase activity. Both mutants completely lost ability to unwind RNA duplexes with 5' overhangs. These findings represent the first report demonstrating NTPase/RNA helicase activity of the helicase domain of HEV ORF1.
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PMID:NTPase and 5' to 3' RNA duplex-unwinding activities of the hepatitis E virus helicase domain. 2007 63

Bacteriophage Phi2954 contains three dsRNA genomic segments, designated L, M, and S. The RNA is located inside a core particle composed of multiple copies of a major structural protein, an RNA-dependent RNA polymerase, a hexameric NTPase, and an auxiliary protein. The core particle is covered by a shell of protein P8, and this structure is enclosed within a lipid-containing membrane. We have found that normal infection of the host Pseudomonas syringae is dependent on the action of a host protein, glutaredoxin 3 (GrxC). GrxC removes the P8 shell from the infecting particle and binds to the inner core. Removal of P8 activates the transcription of segments S and M, whereas binding of GrxC to the core particle activates the transcription of segment L. The differences in transcription behavior are due to the preference of the polymerase for G as the first base of the transcript. Transcripts of segments S and M begin with GCAA, whereas those of segment L begin with ACAA. The binding of GrxC to the particle results in changes in polymerase activity. Mutations resulting in independence of GrxC are found in the gene for protein P1, the major structural protein of the inner core particle.
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PMID:Role of host protein glutaredoxin 3 in the control of transcription during bacteriophage Phi2954 infection. 2023 37


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