3H5S

Hepatitis C virus polymerase NS5B with saccharin inhibitor

3H5S の概要

• エントリーDOI: 10.2210/pdb3h5s/pdb
• 関連するPDBエントリー: 2GIQ 3G86 3H59 3H5U
• 分子名称: RNA-directed RNA polymerase, (5S)-5-tert-butyl-1-(4-fluoro-3-methylbenzyl)-4-hydroxy-3-[8-(methylsulfonyl)-1,1-dioxido-6,7,8,9-tetrahydroisothiazolo[4,5-h]isoquinolin-3-yl]-1,5-dihydro-2H-pyrrol-2-one (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: 129504.65

構造登録者

Harris, S.F.,Wong, A. (登録日: 2009-04-22, 公開日: 2009-09-08, 最終更新日: 2024-11-20)

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.,Adjabeng, G.,Elworthy, T.R.,Li, J.,Wang, B.,Bamberg, J.T.,Harris, S.F.,Wong, A.,Leveque, V.J.,Najera, I.,Le Pogam, S.,Rajyaguru, S.,Ao-Ieong, G.,Alexandrova, L.,Larrabee, S.,Brandl, M.,Briggs, A.,Sukhtankar, S.,Farrell, R.
Non-nucleoside inhibitors of HCV polymerase NS5B. Part 4: structure-based design, synthesis, and biological evaluation of benzo[d]isothiazole-1,1-dioxides
Bioorg.Med.Chem.Lett., 19:5652-5656, 2009

PubMed Abstract: A series of benzo[d]isothiazole-1,1-dioxides were designed and evaluated as inhibitors of HCV polymerase NS5B. Structure-based design led to the incorporation of a high affinity methyl sulfonamide group. Structure-activity relationship (SAR) studies of this series revealed analogues with submicromolar potencies in the HCV replicon assay and moderate pharmacokinetic properties. SAR studies combined with structure based drug design focused on the sulfonamide region led to a novel and potent cyclic analogue.

PubMed: 19709881
DOI: 10.1016/j.bmcl.2009.08.022

実験手法

X-RAY DIFFRACTION (2 Å)