title: The p2gag peptide, AEAMSQVTNTATIM, processed from HIV-1 Pr55gag was found to be a suicide inhibitor of HIV-1 protease.
abstract: The p2gag peptide (AEAMSQVTNTATIM) processed from HIV-1 Pr55gag by HIV-1 protease was identified as a suicide inhibitor of the enzyme (Ki = 30 microM and IC50 = 10 microM for the synthetic peptide substrate, succinyl-SQNYPIVQ), and potently inhibited the proteolytic cleavage of the viral precursor protein (Pr55gag) into functional structural units (p17gag and p24gag) in vitro. The nonapeptide (AEAMSQVTN) derived from N-terminus of the p2gag peptide exhibits a potent inhibitory action on HIV-1 protease, but the other peptides (AEAMSQ, AEAMSQV, AEAMSQVT, VTN and VTNTATIM) do not. It was determined by exclusion gel chromatography that HIV-1 protease after treatment of the synthetic p2gag peptide dissociated from the active dimeric form to an inactive monomeric form. The p2gag peptide and HIV-1 protease were also detected in HIV-1 viral particles using both matrix-assisted laser desorption/ionization time-of-flight mass spectrometric (MALDI TOF-MS) and western immunoblot analyses. Taken together, these results suggest that the p2gag peptide is the inhibitor of preventing dimerization of HIV-1 protease and that the enzyme activity is completely suicide inhibited with the accumulated p2gag peptide producing by the processing of Pr55gag during viral maturation.
authors.affiliation: Department of Biochemistry, Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Misumi
authors.forename: A
authors.initials: A
authors.lastname: Kudo
authors.forename: R
authors.initials: R
authors.lastname: Azuma
authors.forename: M
authors.initials: M
authors.lastname: Tomonaga
authors.forename: K
authors.initials: K
authors.lastname: Furuishi
authors.forename: S
authors.initials: S
authors.lastname: Shoji
mesh_terms: D019281:Dimerization; D015683:Gene Products, gag / Q000378:metabolism / Q000494:pharmacology*; D016333:HIV Protease / Q000187:drug effects* / Q000235:genetics; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000201:enzymology*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology*; D011485:Protein Binding; D011498:Protein Precursors / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000187:drug effects; D054301:gag Gene Products, Human Immunodeficiency Virus
chemical_list: D015683:Gene Products, gag; D017320:HIV Protease Inhibitors; D010446:Peptide Fragments; D011498:Protein Precursors; D011994:Recombinant Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; C109809:p2 gag peptide, Human immunodeficiency virus 1; C059767:p55 gag precursor protein, Human immunodeficiency virus 1; D016333:HIV Protease