Post-translational modification of glutamine and lysine residues of HIV-1 aspartyl protease by transglutaminase increases its catalytic activity

Biochemical and Biophysical Research Communications
Alessandro LentiniS Beninati


The human immunodeficiency virus type 1 aspartyl protease (HIV-1 PR) is a homodimeric aspartyl endopeptidase that is required for virus replication. HIV-1 PR was shown to act invitro as acyl-donor and -acceptor for both guinea pig liver transglutaminase (TG, EC and human Factor XIIIa. These preliminary evidences suggested that the HIV-1 PR contains at least three TG-reactive glutaminyl and one lysyl residues. We report here that the incubation of HIV-1 PR with TG increases its catalytic activity. This increase is dependent upon the time of incubation, the concentration of TG and the presence of Ca2+. Identification of epsilon-(gamma-glutamyl)lysine in the proteolytic digest of the TG-modified HIV-1 PR suggested intramolecular covalent cross-linking of this protease which may promote a non-covalent dimerization and subsequent activation of this enzyme via a conformational change. This hypothesis is supported by the observation that the TG-catalyzed activation of HIV-1 PR was completely abolished by spermidine (SPD) which acts as a competitive inhibitor of epsilon-(gamma-glutamyl)lysine formation. Indeed, in the presence of 1mM SPD the formation of the isopeptide was decreased of about 80%. The main products of the TG-c...Continue Reading


Sep 30, 1992·Biochemical and Biophysical Research Communications·S Beninati, A B Mukherjee
Jul 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·N E KohlI S Sigal
Jan 1, 1980·Annual Review of Biochemistry·J E Folk
Jan 1, 1984·Molecular and Cellular Biochemistry·L Lorand, S M Conrad
May 1, 1994·The Journal of Clinical Investigation·A BergaminiC Amici
Oct 13, 2001·The Journal of Biological Chemistry·R IshimaJ M Louis
Jun 20, 2002·Journal of Immunological Methods·Alessandra AmendolaZsuzsa Szondy
Jun 9, 2004·Journal of Molecular Biology·Yaakov LevyPeter G Wolynes

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