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| Home > Publications database > HIV-1 Integrase Binding to its Cellular Partners: A Perspective from Computational Biology |
| Home > Publications database > HIV-1 Integrase Binding to its Cellular Partners: A Perspective from Computational Biology |
| Journal Article | FZJ-2015-00155 |
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2014
Bentham Science Publ.
Hilversum
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Please use a persistent id in citations: doi:10.2174/13816128113199990631
Abstract: Viral DNA integration into the infected cell genome is an essential step in the HIV-1 life cycle. Hence, the viral integrase enzyme has become an important target for antiviral therapy. The integrase's activity action relies on the binding to its cellular partners, therefore the knowledge of the structural determinants is very important from a therapeutic perspective. Here we first review published computer-aided structural predictions of HIV-1 integrase in complex with its interactors. These include DNA and the human HAT protein. Next, we present a prediction of the complex between HIV-1 integrase with the human prolyl-isomerase-1 (hPin1) enzyme. Interaction with hPin1 is crucial for efficient HIV-1 infection and it increases integrase stability (Manganaro et. al 2010, Nat. Med. 16, 329). The modeling presented here, which is validated against experimental data, provides a rationale for a variety of viral protein's mutations which impair protein function and HIV-1 virus replication in vivo without significantly affecting enzymatic activity.
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