Hepatitis C virus NS3 RNA helicase domain with a bound oligonucleotide: the crystal structure provides insights into the mode of unwinding
Hepatitis C virus NS3 RNA helicase domain with a bound oligonucleotide: the crystal structure provides insights into the mode of unwinding
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DOI：
10.1016/s0969-2126(98)00010-0
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发表时间：
1998-01-15
期刊：
影响因子：
5.7
通讯作者：
Caron, PR
中科院分区：
文献类型：
--
作者：
Kim, JL;Morgenstern, KA;Caron, PR
背景：丙型肝炎病毒（HCV）是一个主要的健康问题，因为它是世界范围内大量肝炎病例的原因。许多研究集中在HCV的复制酶作为更有效的治疗剂的可能靶点。HCV NS3解旋酶可以提供一种这样的合适靶标。解旋酶是能够在ATP依赖性反应中解开DNA或RNA的双链区域的酶。几种解旋酶的结构已被公开，但ATP结合和水解如何与DNA解旋结合的结构细节尚不清楚。与单链DNA寡核苷酸复合的HCV NS3 RNA解旋酶结构域的结构已被解析至2.2埃分辨率，该蛋白由三个结构域组成，寡核苷酸位于前两个结构域和第三个结构域之间的凹槽中。前两个结构域具有腺苷酸激酶样折叠，包括在第一domain.Conclusions磷酸结合环：HCV NS3解旋酶是解旋酶超家族的成员，称为超家族II。在超家族II解旋酶中保守的NS3解旋酶的残基在前两个结构域之间形成结构域间裂缝。寡核苷酸在正交结合位点结合，并接触相对较少的保守残基。与寡核苷酸碱基没有强的序列特异性相互作用。
Background: Hepatitis C virus (HCV) represents a major health concern as it is responsible for a significant number of hepatitis cases worldwide. Much research has focused on the replicative enzymes of HCV as possible targets for more effective therapeutic agents. HCV NS3 helicase may provide one such suitable target. Helicases are enzymes which can unwind double-stranded regions of DNA or RNA in an ATP-dependent reaction. The structures of several helicases have been published but the structural details as to how ATP binding and hydrolysis are coupled to DNA unwinding are unknown.Results: The structure of the HCV NS3 RNA helicase domain complexed with a single-stranded DNA oligonucleotide has been solved to 2.2 Angstrom resolution, The protein consists of three structural domains with the oligonucleotide lying in a groove between the first two domains and the third. The first two domains have an adenylate kinase like fold, including a phosphate-binding loop in the first domain.Conclusions: HCV NS3 helicase is a member of a superfamily of helicases, termed superfamily II. Residues of NS3 helicase which are conserved among superfamily II helicases line an interdomain cleft between the first two domains. The oligonucleotide binds in an orthogonal binding site and contacts relatively few conserved residues. There are no strong sequence-specific interactions with the oligonucleotide bases.