5TRI

CRYSTAL STRUCTURE OF THE HEPATITIS C VIRUS NS5B RNA-DEPENDENT RNA POLYMERASE IN COMPLEX WITH 3-[(4-chlorophenyl)methoxy]-2-(1-oxo-1,3-dihydro-2H-isoindol-2-yl)benzoic acid

5TRI の概要

• エントリーDOI: 10.2210/pdb5tri/pdb
• 関連するPDBエントリー: 5TRH 5TRJ 5TRK
• 分子名称: NS5B RNA-DEPENDENT RNA POLYMERASE, (2E)-3-(4-{[(1-{[(13-cyclohexyl-6-oxo-6,7-dihydro-5H-indolo[1,2-d][1,4]benzodiazepin-10-yl)carbonyl]amino}cyclopentyl)carbonyl]amino}phenyl)prop-2-enoic acid, 3-[(4-chlorophenyl)methoxy]-2-(1-oxo-1,3-dihydro-2H-isoindol-2-yl)benzoic acid, ... (5 entities in total)
• 機能のキーワード: ns5b, polymerase, hcv, fingers, palm, thumb, transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Hepatitis C virus (HCV)
• 細胞内の位置: Core protein p21: Host endoplasmic reticulum membrane ; Single-pass membrane protein . Core protein p19: Virion . Envelope glycoprotein E1: Virion membrane ; Single-pass type I membrane protein . Envelope glycoprotein E2: Virion membrane ; Single-pass type I membrane protein . p7: Host endoplasmic reticulum membrane ; Multi-pass membrane protein . Protease NS2-3: Host endoplasmic reticulum membrane ; Multi-pass membrane protein . Serine protease NS3: Host endoplasmic reticulum membrane ; Peripheral membrane protein . Non-structural protein 4A: Host endoplasmic reticulum membrane ; Single-pass type I membrane protein . Non-structural protein 4B: Host endoplasmic reticulum membrane ; Multi-pass membrane protein . Non-structural protein 5A: Host endoplasmic reticulum membrane ; Peripheral membrane protein . RNA-directed RNA polymerase: Host endoplasmic reticulum membrane ; Single-pass type I membrane protein : Q9WMX2
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 130740.64

構造登録者

Sheriff, S. (登録日: 2016-10-26, 公開日: 2016-11-30, 最終更新日: 2023-10-04)

主引用文献

Parcella, K.,Nickel, A.,Beno, B.R.,Sheriff, S.,Wan, C.,Wang, Y.K.,Roberts, S.B.,Meanwell, N.A.,Kadow, J.F.
Discovery and initial optimization of alkoxyanthranilic acid derivatives as inhibitors of HCV NS5B polymerase.
Bioorg. Med. Chem. Lett., 27:295-298, 2017

PubMed Abstract: Alkoxyanthranilic acid derivatives have been identified to inhibit HCV NS5B polymerase, binding in an allosteric site located at the convergence of the palm and thumb regions. Information from co-crystal structures guided the structural design strategy. Ultimately, two independent structural modifications led to a similar shift in binding mode that when combined led to a synergistic improvement in potency and the identification of inhibitors with sub-micromolar HCV NS5B binding potency.

PubMed: 27908764
DOI: 10.1016/j.bmcl.2016.11.054

実験手法

X-RAY DIFFRACTION (2.3 Å)