3H59

Hepatitis C virus polymerase NS5B with thiazine inhibitor 2

3H59 の概要

• エントリーDOI: 10.2210/pdb3h59/pdb
• 関連するPDBエントリー: 2GIQ 3G86 3H5S 3H5U
• 分子名称: RNA-directed RNA polymerase, N-{3-[(5S)-5-(1,1-dimethylpropyl)-1-(4-fluoro-3-methylbenzyl)-4-hydroxy-2-oxo-2,5-dihydro-1H-pyrrol-3-yl]-1,1-dioxido-4H-1,4-benzothiazin-7-yl}methanesulfonamide (3 entities in total)
• 機能のキーワード: hcv, hepatitis, ns5b, transferase rna-dependent rna polymerase, acetylation, apoptosis, atp-binding, capsid protein, cell membrane, cytoplasm, disulfide bond, endoplasmic reticulum, envelope protein, fusion protein, glycoprotein, helicase, host-virus interaction, hydrolase, interferon antiviral system evasion, lipid droplet, lipoprotein, membrane, metal-binding, mitochondrion, multifunctional enzyme, nucleotide-binding, nucleotidyltransferase, nucleus, oncogene, palmitate, phosphoprotein, protease, ribonucleoprotein, rna replication, rna-binding, rna-directed rna polymerase, secreted, serine protease, sh3-binding, thiol protease, transcription, transcription regulation, transferase, transmembrane, ubl conjugation, viral nucleoprotein, virion, zinc
• 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: 129480.63

構造登録者

Harris, S.F.,Ghate, M. (登録日: 2009-04-21, 公開日: 2009-09-08, 最終更新日: 2024-11-06)

主引用文献

de Vicente, J.,Hendricks, R.T.,Smith, D.B.,Fell, J.B.,Fischer, J.,Spencer, S.R.,Stengel, P.J.,Mohr, P.,Robinson, J.E.,Blake, J.F.,Hilgenkamp, R.K.,Yee, C.,Zhao, J.,Elworthy, T.R.,Tracy, J.,Chin, E.,Li, J.,Lui, A.,Wang, B.,Oshiro, C.,Harris, S.F.,Ghate, M.,Leveque, V.J.,Najera, I.,Le Pogam, S.,Rajyaguru, S.,Ao-Ieong, G.,Alexandrova, L.,Fitch, B.,Brandl, M.,Masjedizadeh, M.,Wu, S.Y.,de Keczer, S.,Voronin, T.
Non-nucleoside inhibitors of HCV polymerase NS5B. Part 3: synthesis and optimization studies of benzothiazine-substituted tetramic acids
Bioorg.Med.Chem.Lett., 19:5648-5651, 2009

PubMed Abstract: Benzothiazine-substituted tetramic acids were discovered as highly potent non-nucleoside inhibitors of HCV NS5B polymerase. X-ray crystallography studies confirmed the binding mode of these inhibitors with HCV NS5B polymerase. Rational optimization of time dependent inactivation of CYP 3A4 and clearance was accomplished by incorporation of electron-withdrawing groups to the benzothiazine core.

PubMed: 19700319
DOI: 10.1016/j.bmcl.2009.08.023

実験手法

X-RAY DIFFRACTION (2.1 Å)