2I1R

Novel Thiazolones as HCV NS5B Polymerase Inhibitors: Further Designs, Synthesis, SAR and X-ray Complex Structure

2I1R の概要

• エントリーDOI: 10.2210/pdb2i1r/pdb
• 関連するPDBエントリー: 2HWH 2HWI
• 分子名称: RNA-directed RNA polymerase (NS5B) (P68), (5Z)-5-[(5-ETHYL-2-FURYL)METHYLENE]-2-{[(S)-(4-FLUOROPHENYL)(1H-TETRAZOL-5-YL)METHYL]AMINO}-1,3-THIAZOL-4(5H)-ONE (3 entities in total)
• 機能のキーワード: hcv, ns5b, viral rna-directed rna polymerase, rdrp, allosteric inhibitor, hcv inhibitor complex, transferase
• 由来する生物種: Hepatitis C virus
• 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: 128823.48

構造登録者

Yao, N.,Yan, S. (登録日: 2006-08-14, 公開日: 2006-10-31, 最終更新日: 2024-02-21)

主引用文献

Yan, S.,Larson, G.,Wu, J.Z.,Appleby, T.,Ding, Y.,Hamatake, R.,Hong, Z.,Yao, N.
Novel thiazolones as HCV NS5B polymerase allosteric inhibitors: Further designs, SAR, and X-ray complex structure.
Bioorg.Med.Chem.Lett., 17:63-67, 2007

PubMed Abstract: Structure-activity relationships (SAR) of 1 against HCV NS5B polymerase were described. SAR explorations and further structure-based design led to the identifications of 2 and 3 as novel HCV NS5B inhibitors. X-ray structure of 3 in complex with NS5B polymerase was obtained at a resolution of 2.2A, and confirmed the design.

PubMed: 17049849
DOI: 10.1016/j.bmcl.2006.09.095

実験手法

X-RAY DIFFRACTION (2.2 Å)