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

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, respec...

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Veröffentlicht in:AIDS (London) 2019-03, Vol.33 (3), p.588-592
Hauptverfasser: Hill, Kyle J, Rogers, Leonard C, Njenda, Duncan T, Burke, Donald H, Sarafianos, Stefan G, Sönnerborg, Anders, Neogi, Ujjwal, Singh, Kamalendra
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Sprache:eng
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Zusammenfassung: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.
ISSN:0269-9370
1473-5571
DOI:10.1097/QAD.0000000000002078