HIV-1 integrase and virus and cell DNAs: complex formation and perturbation by inhibitors of integration.
Neurochem Res
; 35(6): 888-93, 2010 Jun.
Article
em En
| MEDLINE
| ID: mdl-19937113
ABSTRACT
HIV-1 integrase (IN) catalyzes integration of viral DNA into cell DNA through 3'-processing of viral DNA and strand transfer reactions. To learn on binding of IN to DNAs and IN inhibition we applied spectroscopy (circular dichroism, fluorescence) in a simplified model consisting in a peptide analogue (K156) of alpha4 helix involved in recognition of viral and cell DNA; an oligonucleotide corresponding to the U5' LTR DNA end; and an inhibitor (TB11) of the diketo acid (DKA) family. Results extrapolated to IN show that the enzyme binds viral DNA with high affinity and specificity, but cell DNA with low affinity and specificity; the affinity of TB11 for IN is high enough to impair the binding of IN to cell DNA, but not to viral DNA. This explains why TB11 is an inhibitor of strand transfer but not of 3'-processing. These results can help in the search of new IN inhibitors.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
DNA
/
Inibidores de Integrase de HIV
/
Integrase de HIV
Idioma:
En
Revista:
Neurochem Res
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
França