Linked Life Data

9922156

Source:http://linkedlifedata.com/resource/pubmed/id/9922156

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
51
pubmed:dateCreated
1999-2-11
pubmed:abstractText
Retroviral nucleocapsid (NC) proteins contain one or two zinc fingers (ZFs) consisting of a CCHC peptide motif that coordinates Zn(II). Mutational and biochemical analyses have shown that NC ZFs are directly involved in multiple stages of viral replication, including genomic RNA encapsidation, virus maturation, and the early infection process. The multiple roles of the conserved retroviral ZFs make them attractive targets for antiviral agents. We have previously shown that a variety of chemical compounds can inactivate the whole virus by attacking NC ZFs. For the enhancement of the specificity of antiviral reagents, it is desirable to have a detailed knowledge of the spatial organization of reactive sites on the NC protein in its free and oligonucleotide-bound states. A method has been developed using chemical probes to assess the reactivity of specific Cys residues in the NC protein, and is being used to investigate the topography of ZFs in different contexts. In this study we focus on the reaction mechanism of N-ethylmaleimide (NEM) with free HIV-1 NCp7 protein. Our results show that the conformation of free NCp7 restricts the initial site of attack to Cys-49 (the most distal Cys residue in the second ZF) and that the reactivity of thiols in full-length protein differs from that of the isolated ZF peptides. A moderate to near complete reduction in reaction rate was observed when NCp7 was complexed with different oligonucleotides. These findings provide a set of experimentally determined parameters that can serve to guide computational modeling of the NC protein and will be useful for the rational design of drugs directed against retroviral ZFs.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
22
pubmed:volume
37
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
17890-7
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:9922156-Alkylating Agents, pubmed-meshheading:9922156-Amino Acid Sequence, pubmed-meshheading:9922156-Capsid, pubmed-meshheading:9922156-Capsid Proteins, pubmed-meshheading:9922156-Cysteine, pubmed-meshheading:9922156-Ethylmaleimide, pubmed-meshheading:9922156-Fluorescence Polarization, pubmed-meshheading:9922156-Gene Products, gag, pubmed-meshheading:9922156-HIV-1, pubmed-meshheading:9922156-Hydrogen-Ion Concentration, pubmed-meshheading:9922156-Molecular Sequence Data, pubmed-meshheading:9922156-Oligonucleotides, pubmed-meshheading:9922156-Peptide Fragments, pubmed-meshheading:9922156-Protein Conformation, pubmed-meshheading:9922156-Sequence Analysis, pubmed-meshheading:9922156-Viral Proteins, pubmed-meshheading:9922156-Zinc Fingers, pubmed-meshheading:9922156-gag Gene Products, Human Immunodeficiency Virus
pubmed:year
1998
pubmed:articleTitle
Probing the topography of HIV-1 nucleocapsid protein with the alkylating agent N-ethylmaleimide.
pubmed:affiliation
AIDS Vaccine Program, SAIC Frederick, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702, USA. chertova@avpvx1.ncifcrf.gov
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.