4J0A

Crystal structure of hcv ns5b polymerase in complex with 2-{[(4-METHYLPHENYL)SULFONYL]AMINO}-4-PHENOXYBENZOIC ACID

4J0A の概要

• エントリーDOI: 10.2210/pdb4j0a/pdb
• 関連するPDBエントリー: 3MWV 4IZ0 4J02 4J04 4J06 4J08
• 分子名称: Genome polyprotein, 2-{[(4-methylphenyl)sulfonyl]amino}-4-phenoxybenzoic acid (3 entities in total)
• 機能のキーワード: rna-directed rna polymerase, transferase, transferase-transferase inhibitor complex, transferase/transferase 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 (By similarity). 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): O92972
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 128954.69

構造登録者

Coulombe, R. (登録日: 2013-01-30, 公開日: 2013-04-17, 最終更新日: 2023-09-20)

主引用文献

Stammers, T.A.,Coulombe, R.,Rancourt, J.,Thavonekham, B.,Fazal, G.,Goulet, S.,Jakalian, A.,Wernic, D.,Tsantrizos, Y.,Poupart, M.A.,Bos, M.,McKercher, G.,Thauvette, L.,Kukolj, G.,Beaulieu, P.L.
Discovery of a novel series of non-nucleoside thumb pocket 2 HCV NS5B polymerase inhibitors.
Bioorg.Med.Chem.Lett., 23:2585-2589, 2013

PubMed Abstract: A novel series of non-nucleoside thumb pocket 2 HCV NS5B polymerase inhibitors were derived from a fragment-based approach using information from X-ray crystallographic analysis of NS5B-inhibitor complexes and iterative rounds of parallel synthesis. Structure-based drug design strategies led to the discovery of potent sub-micromolar inhibitors 11a-c and 12a-c from a weak-binding fragment-like structure 1 as a starting point.

PubMed: 23545108
DOI: 10.1016/j.bmcl.2013.02.110

実験手法

X-RAY DIFFRACTION (2.4 Å)