INHIBITION OF RETROVIRAL PROTEASE ACTIVITY BY AN ASPARTYL PROTEINASE-INHIBITOR
INHIBITION OF RETROVIRAL PROTEASE ACTIVITY BY AN ASPARTYL PROTEINASE-INHIBITOR
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DOI：
10.1038/329654a0
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发表时间：
1987-10-15
期刊：
影响因子：
64.8
通讯作者：
YOSHINAKA, Y
中科院分区：
文献类型：
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作者：
KATOH, I;YASUNAGA, T;YOSHINAKA, Y
逆转录病毒蛋白酶是一种将gagandgag-pol前体多聚蛋白切割成成熟病毒颗粒功能蛋白的酶1，2。前体多聚蛋白的正确加工对于病毒颗粒的感染性是必要的：在体外诱变中，将缺失引入小鼠白血病病毒基因组，产生不成熟核心形式且缺乏感染性的蛋白酶缺陷型病毒3，4。有效对抗由逆转录病毒增殖引起的疾病的治疗药物同样可以干扰病毒成熟。到目前为止，已经确定了禽成髓细胞瘤病毒5、鼠白血病病毒6、猫白血病病毒7和牛白血病病毒8的蛋白酶的一级结构。逆转录病毒蛋白酶的氨基酸序列，无论是在纯化后还是从核苷酸序列预测，都表明它们具有天冬酰蛋白酶的特征性Asp-Thr-Gly序列。在这份报告中，我们表明，逆转录病毒蛋白酶属于乙酰基蛋白酶组，并证明抑制乙酰基蛋白酶特异性抑制剂，胃酶抑素A，牛白血病，莫洛尼鼠白血病和人类T细胞白血病病毒蛋白酶的活性。
Retrovirus protease is an enzyme that cleavesgagandgag-polprecursor polyproteins into the functional proteins of mature virus particles1,2. The correct processing of precursor polyproteins is necessary for the infectivity of virus particles:in vitromutagenesis which introduces deletions into the murine leukaemia virus genome produces a protease-defective virus of immature core form and lacking infectivity3,4. 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 virus5, and of murine6, feline7and bovine8leukaemia 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 pro-teinases. 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.