Linked Life Data

8617711

Source:http://linkedlifedata.com/resource/pubmed/id/8617711

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
1996-6-11
pubmed:abstractText
The hepatitis delta virus large antigen (lHDAg) is a virally encoded protein that contains a prenylation signal sequence at its carboxyl terminus consisting of the tetrapeptide Cys-Arg-Pro-Gln. Although the presence of the Gln as the COOH-terminal residue generally specifies addition of the 15-carbon farnesyl isoprenoid, earlier reports had suggested that the protein is modified by the 20-carbon geranylgeranyl. The prenylation of lHDAg was examined in vitro using a fusion protein between glutathione S-transferase and the COOH-terminal 117 amino acids of lHDAg (GST-lHDAg). When recombinant GST-lHDAg was incubated with bovine brain cytosol in the presence of either farnesyl diphosphate or geranylgeranyl diphosphate, GST-lHDAg was preferentially farnesylated. Geranylgeranylation of the fusion protein was also observed, although at a rate considerably less than that of farnesylation. Using purified recombinant protein prenyltransferases, GST-lHDAg was found to be an excellent substrate (apparent Km = 0.8 microM) for protein farnesyltransferase (FTase), while modification by protein geranylgeranyltransferase I (GGTase I) was not detected. FTase was also able to catalyze geranylgeranylation of GST-lHDAg at a very low rate, suggesting that the low level of geranylgeranylation of GST-lHDAg observed in cytosolic preparations was mediated by FTase. Consistent with our observations on the in vitro prenylation of the GST-lHDAg fusion protein, isoprenoid analysis of authentic lHDAg expressed in COS cells demonstrated that the protein was farnesylated. Geranylgeranylation of lHDAg expressed in COS cells was not observed. As prenylation of lHDAg is required for the assembly of the hepatitis delta viral particle, these results suggest that inhibitors of FTase may be useful therapeutic agents for treatment of delta virus infection.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
271
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4569-72
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:8617711-Amino Acid Sequence, pubmed-meshheading:8617711-Animals, pubmed-meshheading:8617711-Brain, pubmed-meshheading:8617711-Cattle, pubmed-meshheading:8617711-Cell Line, pubmed-meshheading:8617711-Cercopithecus aethiops, pubmed-meshheading:8617711-Chromatography, High Pressure Liquid, pubmed-meshheading:8617711-Cytosol, pubmed-meshheading:8617711-Dimethylallyltranstransferase, pubmed-meshheading:8617711-Glutathione Transferase, pubmed-meshheading:8617711-Hepatitis Antigens, pubmed-meshheading:8617711-Hepatitis Delta Virus, pubmed-meshheading:8617711-Hepatitis delta Antigens, pubmed-meshheading:8617711-Kinetics, pubmed-meshheading:8617711-Molecular Sequence Data, pubmed-meshheading:8617711-Polyisoprenyl Phosphates, pubmed-meshheading:8617711-Protein Prenylation, pubmed-meshheading:8617711-Recombinant Fusion Proteins, pubmed-meshheading:8617711-Sesquiterpenes, pubmed-meshheading:8617711-Spodoptera, pubmed-meshheading:8617711-Transfection
pubmed:year
1996
pubmed:articleTitle
The hepatitis delta virus large antigen is farnesylated both in vitro and in animal cells.
pubmed:affiliation
Department of Molecular Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710-3686, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.