Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.7 (DNA polymerase)
 17,007 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

6-Methoxypurine arabinoside (ara-M) is a highly selective inhibitor of varicella-zoster virus (VZV). It belongs to a class of purine arabinosides whose anti-VZV activity in vitro correlates with substrate utilization by the VZV-encoded thymidine kinase (TK) (D. R. Averett, G. W. Koszalka, J. A. Fyfe, G. B. Roberts, D. J. M. Purifoy, and T. A. Krenitsky, Antimicrob Agents Chemother. 35:851-857, 1991). In this study, the mechanism of action of ara-M was explored. VZV-infected human fibroblasts selectively accumulated ara-M and its phosphorylated metabolites, whereas in uninfected fibroblasts or in those infected with a TK-deficient strain of VZV, there was virtually no cellular uptake of ara-M. The major intracellular metabolite of ara-M in VZV-infected cells was identified as the triphosphate of adenine arabinoside (ara-ATP). Appreciable levels of ara-ADP, ara-AMP, and ara-MMP were also detected. However, di- or triphosphorylated forms of ara-M were not detected. Moreover, in VZV-infected cells, the concentrations of ara-ATP which accumulated in the presence of ara-M were up to eightfold higher than those generated with ara-A itself. In contrast, in uninfected cells, the levels of ara-ATP which accumulated in the presence of ara-M were barely detectable. Clearly, Ara-M activation was dependent on the activity of the virus-encoded TK, while ara-A anabolism resulted primarily from the activity of host cell enzymes. Therefore, ara-M selectively generates the DNA polymerase inhibitor ara-ATP in the VZV-infected cell.
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PMID:Selective anabolism of 6-methoxypurine arabinoside in varicella-zoster virus-infected cells. 172 79

In order to characterize the genome organization of Xestia c-nigrum granulovirus (XcGV), mapping of putative XcGV genes was performed by construction of lambda and M13 phage libraries followed by Southern blot and nucleotide sequencing analyses. Mapping of the lambda (32 clones covering the entire XcGV genome) and M13 (133 clones made by random cloning) phage library clones was carried out by hybridization of the labeled lambda phage clone DNAs to 1) Southern blotted XcGV genomic DNA fragments cleaved with EcoRI, BamHI, or HindIII, and 2) dot blotted M13 clone DNAs. All 133 M13 clone DNAs were sequenced, and coding possibilities were investigated by computer-assisted homology search; in total, about 43 kb of the genome was sequenced. Amino acid sequence homology searches of 67 M13 clones suggested that these GV DNAs coded for previously characterized genes identified in nucleopolyhedroviruses (NPVs) and GVs. These 67 M13 clones were classified into 25 gene homolog groups (including 29 putative genes) based on their homologies to NPV and GV genes. The remaining M13 clones, except one that encoded a putative metalloproteinase, did not possess deduced amino acid sequences with significant homology to proteins in gene databases. Complete nucleotide sequences of the putative XcGV DNA polymerase and Ac144 homolog genes confirmed the reliability of our speculation of putative genes based on the M13 clones sequencing analysis. In a comparison of relative locations of putative XcGV genes with locations of their homologs in NPVs, most XcGV genes were mapped close to the corresponding locations in NPV genomes. These results suggested that XcGV, compared to NPVs, had relatively conserved gene arrangements, although about 22 kb of 43 kb of DNA sequenced randomly in the XcGV genome consisted of sequences/genes non-homologous to those of previously characterized NPVs.
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PMID:Genome organization of Xestia c-nigrum granulovirus. 960 66