High affinity interaction of HIV-1 integrase with specific and non-specific single-stranded short oligonucleotides.
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 nonspecific. All ODNs were found to competitively inhibit the processing reaction with Ki 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.
Caumont
A
A
EP 630 CNRS-Université Victor Segalen Bordeaux 2, France.
Jamieson
G
G
de Soultrait
V R
VR
Parissi
V
V
Fournier
M
M
Zakharova
O D
OD
Bayandin
R
R
Litvak
S
S
Tarrago-Litvak
L
L
Nevinsky
G A
GA
D017931:DNA Primers; D019427:HIV Integrase / Q000378:metabolism*; D019428:HIV Integrase Inhibitors / Q000494:pharmacology; D016325:HIV Long Terminal Repeat; D007700:Kinetics; D009841:Oligonucleotides / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding; D011499:Protein Processing, Post-Translational
D017931:DNA Primers; D019428:HIV Integrase Inhibitors; D009841:Oligonucleotides; D019427:HIV Integrase