5F41

DENGUE SEROTYPE 3 RNA-DEPENDENT RNA POLYMERASE BOUND TO FD-83-KI26

5F41 の概要

• エントリーDOI: 10.2210/pdb5f41/pdb
• 関連するPDBエントリー: 5F3Z 5FST
• 分子名称: Genome polyprotein, ZINC ION, 2-(4-methoxy-3-thiophen-3-yl-phenyl)ethanoic acid, ... (4 entities in total)
• 機能のキーワード: inhibitor rdrp, dengue virus, transferase
• 由来する生物種: Dengue virus 3
• 細胞内の位置: Virion membrane ; Multi-pass membrane protein : Q6DLV0
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 74003.98

構造登録者

Noble, C.G. (登録日: 2015-12-03, 公開日: 2016-02-24, 最終更新日: 2023-11-08)

主引用文献

Noble, C.G.,Lim, S.P.,Arora, R.,Yokokawa, F.,Nilar, S.,Seh, C.C.,Wright, S.K.,Benson, T.E.,Smith, P.W.,Shi, P.Y.
A Conserved Pocket in the Dengue Virus Polymerase Identified through Fragment-based Screening
J.Biol.Chem., 291:8541-8548, 2016

PubMed Abstract: We performed a fragment screen on the dengue virus serotype 3 RNA-dependent RNA polymerase using x-ray crystallography. A screen of 1,400 fragments in pools of eight identified a single hit that bound in a novel pocket in the protein. This pocket is located in the polymerase palm subdomain and conserved across the four serotypes of dengue virus. The compound binds to the polymerase in solution as evidenced by surface plasmon resonance and isothermal titration calorimetry analyses. Related compounds where a phenyl is replaced by a thiophene show higher affinity binding, indicating the potential for rational design. Importantly, inhibition of enzyme activity correlated with the binding affinity, showing that the pocket is functionally important for polymerase activity. This fragment is an excellent starting point for optimization through rational structure-based design.

PubMed: 26872970
DOI: 10.1074/jbc.M115.710731

実験手法

X-RAY DIFFRACTION (2 Å)