High affinity interaction of HIV‐1 integrase with specific and non‐specific single‐stranded short oligonucleotides

FEBS Letters

Litvak, Simon¹  Nevinsky, Georgy A.²  Bayandin, Roman²  de Soultrait, Vaea Richard¹  Parissi, Vincent¹  Tarrago-Litvak, Laura¹  Caumont, Anne¹  Zakharova, Olga D.²  Fournier, Michel¹  Jamieson, Gordon¹ 

[1] EP 630 CNRS-Université Victor Segalen Bordeaux 2, IFR 66 ‘Pathologies Infectieuses’, 1, rue Camille Saint Saëns, 33077 Bordeaux cedex, France;Novosibirsk Institute of Bioorganic Chemistry, Siberian Division of Russian Academy of Sciences, Novosibirsk 630090, Russia

关键词: HIV-1 integrase;    Specific oligodeoxynucleotide;    Inhibitor;    HIV-1;    human immunodeficiency virus type 1;    IN;    integrase;    LTR;    long terminal repeat;    ODN;    oligodeoxynucleotide;    ss;    single-stranded;    ds;    double-stranded;   

DOI  :  10.1016/S0014-5793(99)00859-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown