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High affinity interaction of HIV‐1 integrase with specific and non‐specific single‐stranded short oligonucleotides
Author(s) -
Caumont Anne,
Jamieson Gordon,
de Soultrait Vaea Richard,
Parissi Vincent,
Fournier Michel,
Zakharova Olga D.,
Bayandin Roman,
Litvak Simon,
Tarrago-Litvak Laura,
Nevinsky Georgy A.
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)00859-5
Subject(s) - integrase , oligonucleotide , dna , long terminal repeat , enzyme , nucleotide , chemistry , hiv long terminal repeat , microbiology and biotechnology , biochemistry , sequence (biology) , biology , genome , gene
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.