3CJ4

Crystal structure of hepatitis c virus rna-dependent rna polymerase ns5b in complex with optimized small molecule fragments

3CJ4 の概要

• エントリーDOI: 10.2210/pdb3cj4/pdb
• 関連するPDBエントリー: 3CIZ 3CJ0 3CJ2 3CJ3 3CJ5
• 分子名称: RNA-directed RNA polymerase, NICKEL (II) ION, 4-[(4-bromo-2-{[(3R,5S)-3,5-dimethylpiperidin-1-yl]carbonyl}phenyl)amino]-4-oxobutanoic acid, ... (4 entities in total)
• 機能のキーワード: drug discovery, hcv ns5b, fragment based, acetylation, apoptosis, atp-binding, capsid protein, cytoplasm, 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 subtype 1b
• 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: 129293.27

構造登録者

Antonysamy, s.s. (登録日: 2008-03-12, 公開日: 2008-04-15, 最終更新日: 2024-02-21)

主引用文献

Antonysamy, S.S.,Aubol, B.,Blaney, J.,Browner, M.F.,Giannetti, A.M.,Harris, S.F.,Hebert, N.,Hendle, J.,Hopkins, S.,Jefferson, E.,Kissinger, C.,Leveque, V.,Marciano, D.,McGee, E.,Najera, I.,Nolan, B.,Tomimoto, M.,Torres, E.,Wright, T.
Fragment-based discovery of hepatitis C virus NS5b RNA polymerase inhibitors.
Bioorg.Med.Chem.Lett., 18:2990-2995, 2008

PubMed Abstract: Non-nucleoside inhibitors of HCV NS5b RNA polymerase were discovered by a fragment-based lead discovery approach, beginning with crystallographic fragment screening. The NS5b binding affinity and biochemical activity of fragment hits and inhibitors was determined by surface plasmon resonance (Biacore) and an enzyme inhibition assay, respectively. Crystallographic fragment screening hits with approximately 1-10mM binding affinity (K(D)) were iteratively optimized to give leads with approximately 200nM biochemical activity and low microM cellular activity in a Replicon assay.

PubMed: 18400495
DOI: 10.1016/j.bmcl.2008.03.056

実験手法

X-RAY DIFFRACTION (2.07 Å)