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)

One of the four genes encoded by hepatitis B virus (HBV) is the regulatory 17 kDa protein called HBx (or pX). HBx is a transcription transactivator of many cellular and viral regulatory elements. We report here that recombinant HBx supports transcription in vitro and has phosphotransfer enzymatic activity. In the presence of EDTA, a phosphoryl-HBx is formed that releases the phosphate residue upon the addition of Mg2+. This two-step NTP hydrolysis reaction is characteristic of a group of enzymes termed nucleoside diphosphate kinases (NDPKs). Remarkably, structural similarity between HBx and NDPKs is also evident. Our findings suggest that HBx has evolved from this group of enzymes but acquired additional activities that satisfy the viral needs.
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PMID:Functional and structural similarity between the X protein of hepatitis B virus and nucleoside diphosphate kinases. 808 7

The hepatitis B virus 17 kDa x gene product expressed in bacteria transactivates a human U6 promoter three- to eightfold in an ATP-independent manner in HeLa cell NTP-depleted extracts containing preassembled transcription preinitiation complexes. However, if added prior to assembly, HBx squelches the promoter. Both the HBx dependent "squelching" of U6 transcription observed in transient transfection analysis, and the transactivation observed in vitro is dependent on the presence of an upstream octamer element. HBx is incorporated via protein-protein interactions into DNA complexes containing the activation domains of Oct-1, and into a stable U6 preinitiation complex. This is consistent with a role as a coactivator interacting with the basal transcription machinery. We propose that the HBx dependent transactivation and repression of U6 transcription occurs by changes in the transcription factor limiting initiation, and propose that HBx may have a dual role in the regulation of transcription in vivo.
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PMID:The 17 kDa HBx protein encoded by hepatitis B virus interacts with the activation domains of Oct-1, and functions as a coactivator in the activation and repression of a human U6 promoter. 817 91

Hepatitis B viruses, or hepadnaviruses, are small DNA-containing viruses that replicate through reverse transcription. Their prototype, HBV, causes severe liver disease in humans. The hepadnaviral P protein is an unusual reverse transcriptase (RT) that initiates DNA synthesis by host-factor-dependent protein priming on a specific RNA stem-loop template, epsilon, yielding a short DNA oligonucleotide covalently attached to the RT. This priming reaction can be reconstituted with in vitro-translated duck hepatitis B virus (DHBV) P protein. No direct structural data are available for any P protein. However, P proteins share a number of conserved motifs with other polymerases. Box A contains an invariant bulky residue recently shown to be crucial for dNTP versus NTP discrimination in RTs and some DNA polymerases; its equivalent in DHBV P protein would be phenylalanine 451 (F451). Four mutants, containing glycine (F451G), alanine (F451A), valine (F451V) and aspartate (F451D), were therefore analyzed for their ability to utilize dNTPs and NTPs in in vitro priming. Priming efficiencies with dNTPs decreased with decreasing side chain size but GTP utilization increased; the wild-type enzyme was inactive with GTP. In the context of complete DHBV genomes, all mutant proteins were competent for RNA encapsidation, indicating the absence of global structural alterations. Because the function of the discriminatory residue depends on its specific spatial disposition this strongly suggests a similar architecture for the P protein dNTP-binding pocket as in other RTs.
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PMID:dNTP versus NTP discrimination by phenylalanine 451 in duck hepatitis B virus P protein indicates a common structure of the dNTP-binding pocket with other reverse transcriptases. 1191 30

The human SUV3gene encodes an NTP-dependent DNA/RNA DExH box helicase predominantly localized in mitochondria. Its orthologue in yeast is a component of the mitochondrial degradosome complex involved in the mtRNA decay pathway. In contrast to this, the physiological function of human SUV3 remains to be elucidated. In this report we demonstrate that the hSuv3 protein interacts with HBXIP, previously identified as a cofactor of survivin in suppression of apoptosis and as a protein that binds the HBx protein encoded by the hepatitis B virus. Using deletion analysis we identified the region within the hSuv3 protein, which is responsible for binding to HBXIP. The HBXIP binding domain was found to be important for mitochondrial import and stability of the Suv3 protein in vivo. We discuss the possible involvement of the hSuv3p-HBXIP interaction in the survivin-dependent antiapoptotic pathway.
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PMID:Human ATP-dependent RNA/DNA helicase hSuv3p interacts with the cofactor of survivin HBXIP. 1617 73

HBx is the smallest gene product of the Hepatitis B virus (HBV) and an oncogenic stimulus in chronic infections leading to liver disease. HBx interacts and interferes with numerous cellular processes, but its modes of action remain poorly understood. It has been invoked that HBx employs nucleotide hydrolysis to regulate molecular pathways or protein-protein interactions. In the present study, we reinvestigate the (d)NTP hydrolysis of recombinant HBx to explore its potential as a biochemical probe for antiviral studies. For our investigations, we employed existing soluble constructs (i.e., GST-HBx, MBP-HBx) and engineered new fusion proteins (i.e., DsbC-HBx, NusA-HBx), which are shown to serve as better systems for in vitro research. We performed mutational scanning of the computationally predicted NTP-binding domain, which includes residues associated with clinical cases. Steady-state and end-point activity assays, in tandem with mass-spectrometric analyses, reveal that the observed hydrolysis of all alleged HBx substrates, ATP, dATP, and GTP, is contingent on the presence of the GroEL chaperone, which preferentially copurifies as a contaminant with GST-HBx and MBP-HBx. Collectively, our findings provide new technical standards for recombinant HBx studies and reveal that nucleotide hydrolysis is not an operant mechanism by which HBx contributes to viral HBV carcinogenesis.
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PMID:Hepatitis B Virus Oncoprotein HBx Is Not an ATPase. 3268 45