Inhibition of retroviral protease activity by an aspartyl proteinase inhibitor.
Retrovirus protease is an enzyme that cleaves gag and gag-pol precursor polyproteins into the functional proteins of mature virus particles. The correct processing of precursor polyproteins is necessary for the infectivity of virus particles: in vitro mutagenesis which introduces deletions into the murine leukaemia virus genome produces a protease-defective virus of immature core form and lacking infectivity. A therapeutic drug effective against disease caused by retrovirus proliferation could likewise interfere with virus maturation. The primary structure has so far been determined for the protease of avian myeloblastosis virus, and of murine, feline and bovine leukaemia viruses. Amino acid sequencing of the retrovirus proteases, either after their purification or from prediction from the nucleotide sequence, shows that they possess the Asp-Thr-Gly sequence characteristic of the aspartyl proteinases. In this report we show that retrovirus proteases belong to the aspartyl proteinase group and demonstrate an inhibition by the aspartyl proteinase-specific inhibitor, pepstatin A, on the activity of bovine leukaemia, Moloney murine leukaemia and human T-cell leukaemia virus proteases.
Katoh
I
I
Laboratory of Molecular Oncology, Tsukuba Life Science Center, Institute of Physical and Chemical Research, Ibaraki, Japan.
Yasunaga
T
T
Ikawa
Y
Y
Yoshinaka
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D016282:Aspartic Acid Endopeptidases; D002851:Chromatography, High Pressure Liquid; D003300:Copper; D017977:Deltaretrovirus / Q000201:enzymology*; D010450:Endopeptidases / Q000378:metabolism*; D015683:Gene Products, gag; D006863:Hydrogen-Ion Concentration; D001909:Leukemia Virus, Bovine / Q000201:enzymology; D008969:Molecular Sequence Data; D008979:Moloney murine leukemia virus / Q000201:enzymology; D009646:Norleucine / Q000031:analogs & derivatives; D010436:Pepstatins / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology*; D011487:Protein Conformation; D011498:Protein Precursors / Q000378:metabolism; D012190:Retroviridae / Q000201:enzymology* / Q000472:pathogenicity; D012191:Retroviridae Proteins / Q000096:biosynthesis; D013379:Substrate Specificity
D015683:Gene Products, gag; D010436:Pepstatins; D011480:Protease Inhibitors; D011498:Protein Precursors; D012191:Retroviridae Proteins; C014195:Streptomyces pepsin inhibitor; C000909:N-diazoacetylnorleucine methyl ester; D003300:Copper; D009646:Norleucine; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C031375:pepstatin