Structure of the HIV-1 integrase catalytic domain complexed with an inhibitor: A platform for antiviral drug design
Structure of the HIV-1 integrase catalytic domain complexed with an inhibitor: A platform for antiviral drug design
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DOI：
10.1073/pnas.96.23.13040
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发表时间：
1999-11-09
影响因子：
11.1
通讯作者：
Davies, DR
中科院分区：
文献类型：
--
作者：
Goldgur, Y;Craigie, R;Davies, DR
HIV整合酶是一种将病毒DNA插入宿主染色体的酶，在哺乳动物中没有对应的酶，这使其成为抗病毒药物设计的一个有吸引力的靶点。作为HIV产生的三种酶之一，可以预期该酶的抑制剂将补充HIV蛋白酶和逆转录酶抑制剂的治疗用途。我们已经确定了HIV-1整合酶核心结构域与新抑制剂5CITEP（1-（5-氯吲哚-3-基）-3-羟基-3-（2 H-四唑-5-基）-丙酮）的复合物的结构，其分辨率为2.1埃。该抑制剂集中结合在整合酶的活性位点，并与蛋白质形成许多紧密接触。蛋白质中只有微小的变化伴随抑制剂结合。这种抑制剂复合物将提供一个平台，用于基于结构的设计的另一类抑制剂的抗病毒治疗。
HIV integrase, the enzyme that inserts the viral DNA into the host chromosome, has no mammalian counterpart, making it an attractive target for antiviral drug design. As one of the three enzymes produced by HIV, it can be expected that inhibitors of this enzyme will complement the therapeutic use of HIV protease and reverse transcriptase inhibitors, We have determined the structure of a complex of the HIV-1 integrase core domain with a novel inhibitor, 5CITEP, 1-(5-chloroindol-3-yl)-3-hydroxy-3-(2H-tetrazole-5-yl)-pro-penone, to 2.1-Angstrom resolution. The inhibitor binds centrally in the active site of the integrase and makes a number of close contacts with the protein. Only minor changes in the protein accompany inhibitor binding. This inhibitor complex will provide a platform for structure-based design of an additional class of inhibitors for antiviral therapy.