High affinity interaction of HIV‐1 integrase with specific and non‐specific single‐stranded short oligonucleotides
Open Access
- 15 July 1999
- journal article
- Published by Wiley in FEBS Letters
- Vol. 455 (1-2), 154-158
- https://doi.org/10.1016/s0014-5793(99)00859-5
Abstract
Retroviral integrase (IN) catalyzes the integration of double‐stranded viral DNA into the host cell genome. The reaction can be divided in two steps: 3′‐end processing and DNA strand transfer. Here we studied the effect of short oligonucleotides (ODNs) on human immunodeficiency virus type 1 (HIV‐1) IN. ODNs were either specific, with sequences representing the extreme termini of the viral long terminal repeats, or non‐specific. All ODNs were found to competitively inhibit the processing reaction with K i values in the nM range for the best inhibitors. Our studies on the interaction of IN with ODNs also showed that: (i) besides the 3′‐terminal GT, the interaction of IN with the remaining nucleotides of the 21‐mer specific sequence was also important for an effective interaction of the enzyme with the substrate; (ii) in the presence of specific ODNs the activity of the enzyme was enhanced, a result which suggests an ODN‐induced conformational change of HIV‐1 IN.Keywords
This publication has 35 references indexed in Scilit:
- Sequence specificity of viral end DNA binding by HIV-1 integrase reveals critical regions for protein-DNA interactionThe EMBO Journal, 1998
- Expression of functional HIV-1 integrase in the yeastSaccharomyces cerevisiae leads to the emergence of a lethal phenotype: potential use for inhibitor screeningCurrent Genetics, 1996
- The Metal Ion-induced Cooperative Binding of HIV-1 Integrase to DNA Exhibits a Marked Preference for Mn(II) Rather than Mg(II)Published by Elsevier ,1996
- High affinity interaction of mammalian DNA topoisomerase I with short single‐ and double‐stranded oligonucleotidesFEBS Letters, 1995
- The human immunodeficiency virus integrase proteinTrends in Genetics, 1993
- Functional analysis of primers and templates in the synthesis of DNA catalyzed by human immunodeficiency virus type 1 reverse transcriptaseEuropean Journal of Biochemistry, 1992
- HIV-1 DNA integration: Mechanism of viral DNA cleavage and DNA strand transferCell, 1991
- Activities of human immunodeficiency virus (HIV) integration protein in vitro: specific cleavage and integration of HIV DNA.Proceedings of the National Academy of Sciences, 1991
- Structure-function analysis of mononucleotides and short oligonucleotides in the priming of enzymic DNA synthesisBiochemistry, 1990
- Protein-nucleic acid interaction in reactions catalyzed with DNA polymerasesBiochimie, 1988