4IH6

Hepatitis C Virus polymerase NS5B (BK) with fragment-based compounds

4IH6 の概要

• エントリーDOI: 10.2210/pdb4ih6/pdb
• 関連するPDBエントリー: 4IH5 4IH7
• 分子名称: RNA-directed RNA polymerase, (5S)-3-(4-tert-butylbenzyl)-5-(propan-2-yl)imidazolidine-2,4-dione (3 entities in total)
• 機能のキーワード: fragment based drug design, 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 (By similarity). Envelope glycoprotein E1: Virion membrane; Single-pass type I membrane protein (Potential). Envelope glycoprotein E2: Virion membrane; Single-pass type I membrane protein (Potential). p7: Host endoplasmic reticulum membrane; Multi-pass membrane protein (By similarity). Protease NS2-3: Host endoplasmic reticulum membrane; Multi-pass membrane protein (Potential). Serine protease NS3: Host endoplasmic reticulum membrane; Peripheral membrane protein (By similarity). Non-structural protein 4A: Host endoplasmic reticulum membrane; Single-pass type I membrane protein (Potential). Non-structural protein 4B: Host endoplasmic reticulum membrane; Multi-pass membrane protein (By similarity). Non-structural protein 5A: Host endoplasmic reticulum membrane; Peripheral membrane protein (By similarity). RNA-directed RNA polymerase: Host endoplasmic reticulum membrane; Single-pass type I membrane protein (Potential): P26663
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 127286.21

構造登録者

Harris, S.F.,Wong, A. (登録日: 2012-12-18, 公開日: 2013-07-03, 最終更新日: 2024-02-28)

主引用文献

Talamas, F.X.,Ao-Ieong, G.,Brameld, K.A.,Chin, E.,de Vicente, J.,Dunn, J.P.,Ghate, M.,Giannetti, A.M.,Harris, S.F.,Labadie, S.S.,Leveque, V.,Li, J.,Lui, A.S.,McCaleb, K.L.,Najera, I.,Schoenfeld, R.C.,Wang, B.,Wong, A.
De novo fragment design: a medicinal chemistry approach to fragment-based lead generation.
J.Med.Chem., 56:3115-3119, 2013

PubMed Abstract: The use of fragments with low binding affinity for their targets as starting points has received much attention recently. Screening of fragment libraries has been the most common method to find attractive starting points. Herein, we describe a unique, alternative approach to generating fragment leads. A binding model was developed and a set of guidelines were then selected to use this model to design fragments, enabling our discovery of a novel fragment with high LE.

PubMed: 23509929
DOI: 10.1021/jm4002605

実験手法

X-RAY DIFFRACTION (2.2 Å)