CRYSTAL-STRUCTURE OF A RETROVIRAL PROTEASE PROVES RELATIONSHIP TO ASPARTIC PROTEASE FAMILY
CRYSTAL-STRUCTURE OF A RETROVIRAL PROTEASE PROVES RELATIONSHIP TO ASPARTIC PROTEASE FAMILY
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DOI：
10.1038/337576a0
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发表时间：
1989-02-09
期刊：
影响因子：
64.8
通讯作者：
WLODAWER, A
中科院分区：
文献类型：
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作者：
MILLER, M;JASKOLSKI, M;WLODAWER, A
逆转录病毒基因的产物被翻译成前体多蛋白，这些前体多蛋白被病毒编码的蛋白酶切割，产生在病毒颗粒中发现的成熟蛋白1 - 11。根据推测的蛋白酶活性位点上保守的Asp-Thr / Ser-Gly序列，以及其他生化证据2,3,12 - 16，逆转录病毒蛋白酶被预测属于胃蛋白酶样天冬氨酸蛋白酶家族。有人认为，天冬氨酸蛋白酶是从一种较小的二聚体祖先蛋白进化而来的，最近的人类免疫缺陷病毒（HIV）蛋白酶模型假设，这种酶的对称二聚体相当于类似于蛋白酶的天冬氨酸蛋白酶18。我们现在已经确定了劳斯肉瘤病毒（RSV）蛋白酶在3-Å分辨率下的晶体结构，发现它是二聚体，具有与天冬氨酸蛋白酶相似的结构19 - 22。该结构为其他逆转录病毒蛋白酶（如HIV）的结构建模提供了有益的基础，也为合理设计蛋白酶抑制剂作为潜在的抗病毒药物提供了有益的基础。
Retroviralgag,polandenvgene products are translated as precursor polyproteins, which are cleaved by virus-encoded proteases to produce the mature proteins found in virions1–11. On the basis of the conserved Asp—Thr/Ser—Gly sequence at the putative protease active sites, and other biochemical evidence2,3,12–16, retroviral proteases have been predicted to be in the family of pepsin-like aspartic proteases. It has been suggested that aspartic proteases evolved from a smaller, dimeric ancestral protein17, and a recent model of the human immunodeficiency virus (HIV) protease postulated that a symmetric dimer of this enzyme is equivalent to a pepsin-like aspartic protease18. We have now determined the crystal structure of Rous sarcoma virus (RSV) protease at 3-Å resolution and find it is dimeric and has a structure similar to aspartic proteases19–22. This structure should provide a useful basis for the modelling of the structures of other retroviral proteases, such as that of HIV, and also for the rational design of protease inhibitors as potential antiviral drugs.