Katoh I, Yasunaga T, Ikawa Y, Yoshinaka Y
Laboratory of Molecular Oncology, Tsukuba Life Science Center, Institute of Physical and Chemical Research, Ibaraki, Japan.
Nature. 1987;329(6140):654-6. doi: 10.1038/329654a0.
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.
逆转录病毒蛋白酶是一种将gag和gag-pol前体多聚蛋白切割成成熟病毒颗粒功能蛋白的酶。前体多聚蛋白的正确加工对于病毒颗粒的感染性至关重要：在体外诱变中，将缺失引入小鼠白血病病毒基因组会产生一种未成熟核心形式且缺乏感染性的蛋白酶缺陷型病毒。一种有效对抗由逆转录病毒增殖引起疾病的治疗药物同样可能干扰病毒成熟。到目前为止，已经确定了禽成髓细胞瘤病毒以及小鼠、猫和牛白血病病毒蛋白酶的一级结构。逆转录病毒蛋白酶的氨基酸测序，无论是在纯化后还是根据核苷酸序列预测，都表明它们具有天冬氨酸蛋白酶特有的Asp-Thr-Gly序列。在本报告中，我们表明逆转录病毒蛋白酶属于天冬氨酸蛋白酶组，并证明天冬氨酸蛋白酶特异性抑制剂胃蛋白酶抑制剂A对牛白血病、莫洛尼氏小鼠白血病和人类T细胞白血病病毒蛋白酶的活性具有抑制作用。
