通过与抑制剂的复合物揭示登革热病毒 RNA 依赖性 RNA 聚合酶的构象灵活性。
Conformational flexibility of the Dengue virus RNA-dependent RNA polymerase revealed by a complex with an inhibitor.
机构信息
Novartis Institute for Tropical Diseases, Singapore, Singapore.
出版信息
J Virol. 2013 May;87(9):5291-5. doi: 10.1128/JVI.00045-13. Epub 2013 Feb 13.
Abstract
We report a highly reproducible method to crystallize the RNA-dependent RNA polymerase (RdRp) domain of dengue virus serotype 3 (DENV-3), allowing structure refinement to a 1.79-Å resolution and revealing amino acids not seen previously. We also present a DENV-3 polymerase/inhibitor cocrystal structure at a 2.1-Å resolution. The inhibitor binds to the RdRp as a dimer and causes conformational changes in the protein. The improved crystallization conditions and new structural information should accelerate structure-based drug discovery.
摘要
我们报告了一种高度可重复的方法来结晶登革热病毒 3 型（DENV-3）的 RNA 依赖性 RNA 聚合酶（RdRp）结构域，允许结构精修至 1.79 Å 的分辨率，并揭示了以前未见过的氨基酸。我们还展示了一个分辨率为 2.1 Å 的 DENV-3 聚合酶/抑制剂共晶结构。抑制剂以二聚体形式结合到 RdRp 上，并导致蛋白质构象发生变化。改进的结晶条件和新的结构信息应加速基于结构的药物发现。
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