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Strain-specific effect on biphasic DNA binding by HIV-1 integrase.

ABSTRACT: : The oligomerization of HIV-1 integrase onto DNA is not well understood. Here we show that HIV-1 integrase binds the DNA in biphasic (high-affinity and low-affinity) modes. For HIV-1 subtype B, the high-affinity mode is ?100-fold greater than the low-affinity mode (Kd.DNA?=?37 and 3400?nmol/l, respectively). The Kd.DNA values of patient-derived integrases containing subtype-specific polymorphisms were affected two- to four-fold, suggesting that polymorphisms may have an influence on effective-concentrations of inhibitors, as these inhibitors preferably bind to integrase-DNA complex.

SUBMITTER: Hill KJ

PROVIDER: S-EPMC6472922 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Strain-specific effect on biphasic DNA binding by HIV-1 integrase.

Hill Kyle J KJ Rogers Leonard C LC Njenda Duncan T DT Burke Donald H DH Sarafianos Stefan G SG Sönnerborg Anders A Neogi Ujjwal U Singh Kamalendra K

AIDS (London, England) 20190301 3

: The oligomerization of HIV-1 integrase onto DNA is not well understood. Here we show that HIV-1 integrase binds the DNA in biphasic (high-affinity and low-affinity) modes. For HIV-1 subtype B, the high-affinity mode is ∼100-fold greater than the low-affinity mode (Kd.DNA = 37 and 3400 nmol/l, respectively). The Kd.DNA values of patient-derived integrases containing subtype-specific polymorphisms were affected two- to four-fold, suggesting that polymorphisms may have an influence on effective-c ...[more]

PMID: 30475264

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