Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A sequence of 3299 nt, contiguous with the previously sequenced quinate permease-encoding (qutD) gene and encompassing the dehydroshikimate dehydratase-encoding (qutC) gene, has been determined. Northern-blot analysis detected (i) a quinate-inducible mRNA of the expected size for the qutC gene, and (ii) a quinate-inducible mRNA of 1.45 kb divergently transcribed away from qutC towards qutD. Computer-aided sequence analysis identified an ORF of 1047 nt corresponding to the qutC gene encoding dehydroshikimate dehydratase. In addition, a genetically uncharacterized 1188-nt gene, designated qutH and containing a putative intron of 61 nt, was identified between qutC and qutD. The inferred protein sequence encoded by qutH contains a putative 'zinc cluster' motif and has a low (16%) but significant similarity with the DNA-directed DNA polymerase of hepatitis B virus. The results are interpreted as being consistent with the view that the qutH gene encodes a DNA-binding protein, possibly involved in the regulation of genes essential for the utilisation of protocatechuic acid.
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PMID:A second gene (qutH) within the Aspergillus nidulans-quinic-acid utilisation gene cluster encodes a protein with a putative zinc-cluster motif. 133 61

We have used the endogenous reverse transcriptase reaction of viral core particles from duck liver to elucidate the mechanism of inhibition of duck hepatitis B virus (DHBV) replication by the nucleoside analog (-)-beta-L-2',3'-dideoxy-3'-thiacytidine (3TC). As is the case in human immunodeficiency virus replication, 3TC-5'-triphosphate (3TC-TP) acts as a chain terminator for the DNA polymerase activities. The results of several different experiments support this conclusion, which explains the potent activity of 3TC against the hepadnaviruses. In isolated DHBV core particles, 3TC-TP inhibited the reverse transcriptase in a manner that resembled competitive inhibition with respect to dCTP. However, the kinetics of inhibition was not linear on a double-reciprocal plot for the highest concentrations of 3TC-TP and the lowest concentration of dCTP. This anomaly would be expected if binding to the nucleotide site was followed by DNA chain termination. Calculations that used only the linear part of the curve yielded a Ki of 0.78 +/- 0.10 microM 3TC-TP. The inhibition of core particles incubated in vitro with 3TC-TP was not reversed by removal of the free inhibitor. 3TC-TP inactivated the reverse transcriptase activity in a concentration-dependent manner. The Km of the chain termination reaction was calculated at 0.71 +/- 0.05 microM. Similar competitive kinetics and irreversible inhibition were also obtained on the endogenous DNA polymerase from viral particles from serum, suggesting that 3TC-TP also acts as a chain terminator of the DNA-directed DNA polymerase of DHBV replication.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanism of inhibition of duck hepatitis B virus polymerase by (-)-beta-L-2',3'-dideoxy-3'-thiacytidine. 749 80

The duck hepatitis B virus (DHBV) genome contains a pol gene that codes for the viral polymerase protein. This enzyme, which is essential for the replication of the virus, has multiple activities including an RNA directed DNA polymerase or reverse transcriptase (RT) activity, an RNase H activity, and a DNA-directed DNA polymerase activity. The assay described in this chapter is designed to measure the ability of test compounds to inhibit the RNA-directed DNA polymerase activity of the DHBV pol gene product. The assay is based on research performed in the laboratory of Dr. Christoph Seeger (1) and on the observation that the e stem loop structure in the pregenomic RNA is required for initiation of DNA synthesis (2-4).
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PMID:A rapid microtiter assay for duck hepatitis virus reverse transcriptase. 2133