PMID: 9557677Apr 29, 1998Paper

Mutational scan of the human immunodeficiency virus type 2 integrase protein

Journal of Virology
F M van den EntR H Plasterk

Abstract

Retroviral integrase (IN) cleaves linear viral DNA specifically near the ends of the DNA (cleavage reaction) and subsequently couples the processed ends to phosphates in the target DNA (integration reaction). In vitro, IN catalyzes the disintegration reaction, which is the reverse of the integration reaction. Ideally, we would like to test the role of each amino acid in the IN protein. We mutagenized human immunodeficiency virus type 2 IN in a random way using PCR mutagenesis and generated a set of mutants in which 35% of all residues were substituted. Mutant proteins were tested for in vitro activity, e.g., site-specific cleavage of viral DNA, integration, and disintegration. Changes in 61 of the 90 proteins investigated showed no phenotypic effect. Substitutions that changed the choice of nucleophile in the cleavage reaction were found. These clustered around the active-site residues Asp-116 and Glu-152. We also found alterations of amino acids that affected cleavage and integration differentially. In addition, we analyzed the disintegration activity of the proteins and found substitutions of amino acids close to the dimer interface that enhanced intermolecular disintegration activity, whereas other catalytic activities were ...Continue Reading

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Citations

Nov 5, 1999·Annual Review of Microbiology·L HarenM Chandler
Oct 25, 2002·AIDS Research and Human Retroviruses·Cara Carthel BurnsJulie Overbaugh
Jun 11, 2003·The Journal of Biological Chemistry·Goedele MaertensYves Engelborghs
Sep 27, 2005·Journal of Computer-aided Molecular Design·Jerome WielensDavid K Chalmers
Mar 5, 2013·International Journal of Molecular Sciences·Pascal Obong Bessong, Julius Nwobegahay
Jul 3, 2013·PLoS Pathogens·Suzannah J RihnPaul D Bieniasz

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