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

Abstract

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 2.3.2.13) 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

References

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Related Concepts

N(1)-(gamma-glutamyl)spermidine
Catalysis
Enzyme Activation
D-Glutamine
Cavia porcellus
Liver
Lysine Hydrochloride
Post-Translational Protein Processing
Transglutaminases
Spermidine

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