HIV-1 integrase binding to its cellular partners: a perspective from computational biology. Curr Pharm Des 2014;20(21):3412-21
Date
09/05/2013Pubmed ID
24001231DOI
10.2174/13816128113199990631Scopus ID
2-s2.0-84903727821 (requires institutional sign-in at Scopus site) 2 CitationsAbstract
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.
Author List
Quy VC, Carnevale V, Manganaro L, Lusic M, Rossetti G, Leone V, Fenollar-Ferrer C, Raugei S, Del Sal G, Giacca M, Carloni PAuthor
Vanessa Leone PhD Assistant Professor in the Biophysics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Computational BiologyDNA
HIV Integrase
Histone Acetyltransferases
Humans
Models, Molecular
NIMA-Interacting Peptidylprolyl Isomerase
Peptidylprolyl Isomerase
Protein Binding
Virus Integration
