4KB7

HCV NS5B GT1B N316Y with CMPD 32

4KB7 の概要

• エントリーDOI: 10.2210/pdb4kb7/pdb
• 関連するPDBエントリー: 4KAI 4KBI 4KE5 4KHM 4KHR
• 分子名称: HCV Polymerase, 5-cyclopropyl-2-(4-fluorophenyl)-6-[{2-[(3R)-1-hydroxy-1,3-dihydro-2,1-benzoxaborol-3-yl]ethyl}(methylsulfonyl)amino]-N-methyl-1-benzofuran-3-carboxamide (3 entities in total)
• 機能のキーワード: hcv polymerase, hcv ns5b, site iv inhibitor, boron, p66, p70, rna directed rna polymerase, tar7360, rna-dependent rna polymerase, replication-replication inhibitor complex, replication/replication 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: 130495.12

構造登録者

Williams, S.P.,Kahler, K.M.,Shotwell, J.B. (登録日: 2013-04-23, 公開日: 2013-05-08, 最終更新日: 2024-03-13)

主引用文献

Maynard, A.,Crosby, R.M.,Ellis, B.,Hamatake, R.,Hong, Z.,Johns, B.A.,Kahler, K.M.,Koble, C.,Leivers, A.,Leivers, M.R.,Mathis, A.,Peat, A.J.,Pouliot, J.J.,Roberts, C.D.,Samano, V.,Schmidt, R.M.,Smith, G.K.,Spaltenstein, A.,Stewart, E.L.,Thommes, P.,Turner, E.M.,Voitenleitner, C.,Walker, J.T.,Waitt, G.,Weatherhead, J.,Weaver, K.,Williams, S.,Wright, L.,Xiong, Z.Z.,Haigh, D.,Shotwell, J.B.
Discovery of a Potent Boronic Acid Derived Inhibitor of the HCV RNA-Dependent RNA Polymerase.
J.Med.Chem., 57:1902-1913, 2014

PubMed Abstract: A boronic acid moiety was found to be a critical pharmacophore for enhanced in vitro potency against wild-type hepatitis C replicons and known clinical polymorphic and resistant HCV mutant replicons. The synthesis, optimization, and structure-activity relationships associated with inhibition of HCV replication in a subgenomic replication system for a series of non-nucleoside boron-containing HCV RNA-dependent RNA polymerase (NS5B) inhibitors are described. A summary of the discovery of 3 (GSK5852), a molecule which entered clinical trials in subjects infected with HCV in 2011, is included.

PubMed: 23672667
DOI: 10.1021/jm400317w

実験手法

X-RAY DIFFRACTION (1.85 Å)