Linked Life Data

7525567

Source:http://linkedlifedata.com/resource/pubmed/id/7525567

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
45
pubmed:dateCreated
1994-12-16
pubmed:abstractText
The K65R mutation in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) encodes cross-resistance to 2',3'-dideoxycytidine (ddC), 2',3'-dideoxy-3'-thiacytidine (3TC), and 2',3'-dideoxyinosine (ddI). We characterized the in vitro sensitivities of recombinant wild type (wt) and K65R mutant RT to dideoxynucleoside triphosphate (ddNTP) inhibitors, using a variety of primer-templates. With poly(rA)-oligo(dT), the K65R mutant showed slight increases in Ki for ddTTP and 3'-azido, 3'-deoxythymidine triphosphate (AZTTP) compared to wt RT, but neither wt nor K65R RT was inhibited by ddCTP or ddATP. With poly(rI)-oligo(dC), the K65R mutant showed a 2-fold increase in Km for dCTP and a 20-fold increase in Ki for ddCTP compared to wt, whereas ddATP, ddTTP, and AZTTP failed to inhibit either enzyme. With a heteropolymeric primer-template, the K65R mutant showed 10-fold reduced sensitivities to ddCTP, 3TCTP, and ddATP, and 4-fold reduced sensitivity to AZTTP, compared to wt. In contrast, both enzymes were equally inhibited by ddTTP and ddGTP. HIV-1 cross-resistance to ddC/3TC/ddI resulting from the K65R mutation may therefore involve selective alterations in substrate/inhibitor recognition. Additionally, competitive inhibition by ddNTPs noncomplementary to the template base appears to be unimportant in the mechanism of inhibition of HIV-1 RT by dideoxynucleoside analogs.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
11
pubmed:volume
269
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
28118-22
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:7525567-Amino Acid Sequence, pubmed-meshheading:7525567-Antiviral Agents, pubmed-meshheading:7525567-Base Sequence, pubmed-meshheading:7525567-Cloning, Molecular, pubmed-meshheading:7525567-DNA Primers, pubmed-meshheading:7525567-Didanosine, pubmed-meshheading:7525567-Drug Resistance, Microbial, pubmed-meshheading:7525567-HIV Reverse Transcriptase, pubmed-meshheading:7525567-HIV-1, pubmed-meshheading:7525567-Kinetics, pubmed-meshheading:7525567-Lamivudine, pubmed-meshheading:7525567-Molecular Sequence Data, pubmed-meshheading:7525567-Mutagenesis, Site-Directed, pubmed-meshheading:7525567-Point Mutation, pubmed-meshheading:7525567-Polynucleotides, pubmed-meshheading:7525567-RNA-Directed DNA Polymerase, pubmed-meshheading:7525567-Recombinant Proteins, pubmed-meshheading:7525567-Reverse Transcriptase Inhibitors, pubmed-meshheading:7525567-Substrate Specificity, pubmed-meshheading:7525567-Templates, Genetic, pubmed-meshheading:7525567-Zalcitabine
pubmed:year
1994
pubmed:articleTitle
The K65R mutant reverse transcriptase of HIV-1 cross-resistant to 2', 3'-dideoxycytidine, 2',3'-dideoxy-3'-thiacytidine, and 2',3'-dideoxyinosine shows reduced sensitivity to specific dideoxynucleoside triphosphate inhibitors in vitro.
pubmed:affiliation
Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, Montreal, Quebec, Canada.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't