The catalytic domain of human immunodeficiency virus integrase: Ordered active site in the F185H mutant
The catalytic domain of human immunodeficiency virus integrase: Ordered active site in the F185H mutant
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DOI：
10.1016/s0014-5793(96)01236-7
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发表时间：
1996-12-02
期刊：
影响因子：
3.5
通讯作者：
Wlodawer, A
中科院分区：
文献类型：
--
作者：
Bujacz, G;Alexandratos, J;Wlodawer, A
我们解析了结构并追踪了具有 F185H 突变的人类免疫缺陷病毒 1 型整合酶 (HIV-1 IN) 催化结构域的完整活性位点。之前唯一可用的晶体结构，即该结构域的 F185K 突变体，缺少催化重要残基之一 E152，该残基位于一段 12 个无序残基中 [Dyda 等人，(1994) Science 266， 1981-1986]，然而，很明显，在任一结构中观察到的 HIV-1 IN 活性位点都不能与功能酶的活性位点相对应，因为三个保守羧酸的簇不能产生适当的金属结合位点。将环的构象与相关禽肉瘤病毒整合酶催化结构域中发现的两种不同构象进行比较[Bujacz 等人，2017]。 (1995) J.摩尔。生物。 253、333-346]。为了使酶在底物和/或辅因子存在下呈现功能构象，可能需要整合酶活性位点区域的灵活性。
We solved the structure and traced the complete active site of the catalytic domain of the human immunodeficiency virus type 1 integrase (HIV-1 IN) with the F185H mutation, The only previously available crystal structure, the F185K mutant of this domain, lacks one of the catalytically important residues, E152, located in a stretch of 12 disordered residues [Dyda et al, (1994) Science 266, 1981-1986], It is clear, however, that the active site of HIV-1 IN observed in either structure cannot correspond to that of the functional enzyme, since the cluster of three conserved carboxylic acids does not create a proper metal-binding site. The conformation of the loop was compared with two different conformations found in the catalytic domain of the related avian sarcoma virus integrase [Bujacz et al. (1995) J. Mol. Biol. 253, 333-346]. Flexibility of the active site region of integrases may be required in order for the enzyme to assume a functional conformation in the presence of substrate and/or cofactors.