CONSERVED FOLDING IN RETROVIRAL PROTEASES - CRYSTAL-STRUCTURE OF A SYNTHETIC HIV-1 PROTEASE
CONSERVED FOLDING IN RETROVIRAL PROTEASES - CRYSTAL-STRUCTURE OF A SYNTHETIC HIV-1 PROTEASE
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DOI：
10.1126/science.2548279
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发表时间：
1989-08-11
期刊：
影响因子：
56.9
通讯作者：
KENT, SBH
中科院分区：
文献类型：
--
作者：
WLODAWER, A;MILLER, M;KENT, SBH
能够抑制病毒蛋白酶作用的药物的合理设计依赖于获得这些酶的精确结构。化学合成的HIV-1蛋白酶的晶体结构已被确定在2.8埃分辨率（R因子为0.184）与使用一个模型的基础上劳斯肉瘤病毒蛋白酶的结构。在这种具有酶活性的蛋白质中，半胱氨酸被α-氨基-正丁酸（一种非遗传编码的氨基酸）取代。这种结构，其中所有99个氨基酸的位置，在几个重要的细节不同于以前报道的其他人。形成活性蛋白酶二聚体的相同亚基之间的界面由来自氨基和羧基末端的四条有序的β链组成，并且残基86至94具有螺旋构象。所观察到的二聚体界面的安排表明可能的二聚化抑制剂的设计。
The rational design of drugs that can inhibit the action of viral proteases depends on obtaining accurate structures of these enzymes. The crystal structure of chemically synthesized HIV-1 protease has been determined at 2.8 angstrom resolution (Rfactor of 0.184) with the use of a model based on the Rous sarcoma virus protease structure. In this enzymatically active protein, the cysteines were replaced by α-amino-n-butyric acid, a nongenetically coded amino acid. This structure, in which all 99 amino acids were located, differs in several important details from that reported previously by others. The interface between the identical subunits forming the active protease dimer is composed of four well-ordered β strands from both the amino and carboxyl termini and residues 86 to 94 have a helical conformation. The observed arrangement of the dimer interface suggests possible designs for dimerization inhibitors.