2O5D

Thiazolone-acylsulfonamides as novel HCV NS5B polymerase allosteric inhibitors: Convergence of structure-based drug design and X-ray crystallographic study

2O5D の概要

• エントリーDOI: 10.2210/pdb2o5d/pdb
• 分子名称: HCV, (2S)-2-({(5Z)-5-[(5-ETHYL-2-FURYL)METHYLENE]-4-OXO-4,5-DIHYDRO-1,3-THIAZOL-2-YL}AMINO)-2-(4-FLUOROPHENYL)-N-[(4-NITROPHENYL)SULFONYL]ACETAMIDE (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, structure-based drug design, viral protein
• 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: 129143.77

構造登録者

Yao, N. (登録日: 2006-12-05, 公開日: 2007-02-20, 最終更新日: 2023-12-27)

主引用文献

Yan, S.,Appleby, T.,Larson, G.,Wu, J.Z.,Hamatake, R.K.,Hong, Z.,Yao, N.
Thiazolone-acylsulfonamides as novel HCV NS5B polymerase allosteric inhibitors: Convergence of structure-based drug design and X-ray crystallographic study.
Bioorg.Med.Chem.Lett., 17:1991-1995, 2007

PubMed Abstract: A novel series of thiazolone-acylsulfonamides were designed as HCV NS5B polymerase allosteric inhibitors. The structure based drug designs (SBDD) were guided by docking results that revealed the potential to explore an additional pocket in the allosteric site. In particular, the designed molecules contain moieties of previously described thiazolone and a newly designed acylsulfonamide linker that is in turn connected with a substituted aromatic ring. The selected compounds were synthesized and demonstrated low muM activity. The X-ray complex structure was determined at a 2.2A resolution and converged with the SBDD principle.

PubMed: 17276060
DOI: 10.1016/j.bmcl.2007.01.024

実験手法

X-RAY DIFFRACTION (2.2 Å)