5CZB

HCV NS5B IN COMPLEX WITH LIGAND IDX17119-5

5CZB の概要

• エントリーDOI: 10.2210/pdb5czb/pdb
• 分子名称: NS5B, 1-[4-(7-amino-5-methylpyrazolo[1,5-a]pyrimidin-2-yl)phenyl]-3-{[(R)-(2,4-dimethylphenyl)(methoxy)phosphoryl]amino}-1H-pyrazole-4-carboxylic acid, GLYCEROL, ... (7 entities in total)
• 機能のキーワード: hcv polymerase, idenix, inhibitor, proteros biostructures gmbh, replication
• 由来する生物種: Hepatitis C virus subtype 1b (HCV)
• 細胞内の位置: Core protein p21: Host endoplasmic reticulum membrane ; Single-pass membrane protein . Core protein p19: Virion . Envelope glycoprotein E1: Virion membrane ; Single-pass type I membrane protein . Envelope glycoprotein E2: Virion membrane ; Single-pass type I membrane protein . p7: Host endoplasmic reticulum membrane ; Multi-pass membrane protein . Protease NS2-3: Host endoplasmic reticulum membrane ; Multi-pass membrane protein . Serine protease NS3: Host endoplasmic reticulum membrane ; Peripheral membrane protein . Non-structural protein 4A: Host endoplasmic reticulum membrane ; Single-pass type I membrane protein . Non-structural protein 4B: Host endoplasmic reticulum membrane ; Multi-pass membrane protein . Non-structural protein 5A: Host endoplasmic reticulum membrane ; Peripheral membrane protein . RNA-directed RNA polymerase: Host endoplasmic reticulum membrane ; Single-pass type I membrane protein : O92972
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 129021.89

構造登録者

Pierra, C.,Dousson, C.,Augustin, M. (登録日: 2015-07-31, 公開日: 2016-06-15, 最終更新日: 2024-05-01)

主引用文献

Pierra Rouviere, C.,Amador, A.,Badaroux, E.,Convard, T.,Da Costa, D.,Dukhan, D.,Griffe, L.,Griffon, J.F.,LaColla, M.,Leroy, F.,Liuzzi, M.,Loi, A.G.,McCarville, J.,Mascia, V.,Milhau, J.,Onidi, L.,Paparin, J.L.,Rahali, R.,Sais, E.,Seifer, M.,Surleraux, D.,Standring, D.,Dousson, C.
Synthesis of potent and broad genotypically active NS5B HCV non-nucleoside inhibitors binding to the thumb domain allosteric site 2 of the viral polymerase.
Bioorg.Med.Chem.Lett., 26:4536-4541, 2016

PubMed Abstract: The hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase (RdRp) plays a central role in virus replication. NS5B has no functional equivalent in mammalian cells and, as a consequence, is an attractive target for selective inhibition. This Letter describes the discovery of a new family of HCV NS5B non-nucleoside inhibitors, based on the bioisosterism between amide and phosphonamidate functions. As part of this program, SAR in this new series led to the identification of IDX17119, a potent non-nucleoside inhibitor, active on the genotypes 1b, 2a, 3a and 4a. The structure and binding domain of IDX17119 were confirmed by X-ray co-crystallization study.

PubMed: 27520942
DOI: 10.1016/j.bmcl.2016.01.042

実験手法

X-RAY DIFFRACTION (1.96 Å)