3QGG

Crystal structure of the hepatitis C virus NS5B RNA-dependent RNA polymerase complex with (2E)-3-(4-{[(1-{[(13-cyclohexyl-6-oxo-6,7-dihydro-5H-indolo[1,2-d][1,4]benzodiazepin-10-yl)carbonyl]amino}cyclopentyl)carbonyl]amino}phenyl)prop-2-enoic acid and N-cyclopropyl-6-[(3R)-3-{[4-(trifluoromethoxy)benzyl]carbamoyl}-4-{[4-(trifluoromethoxy)phenyl]sulfonyl}piperazin-1-yl]pyridazine-3-carboxamide

3QGG の概要

• エントリーDOI: 10.2210/pdb3qgg/pdb
• 関連するPDBエントリー: 3QGD 3QGE 3QGF 3QGH 3QGI
• 分子名称: RNA-directed RNA polymerase, (2E)-3-(4-{[(1-{[(13-cyclohexyl-6-oxo-6,7-dihydro-5H-indolo[1,2-d][1,4]benzodiazepin-10-yl)carbonyl]amino}cyclopentyl)carbonyl]amino}phenyl)prop-2-enoic acid, N-cyclopropyl-6-[(3R)-3-{[4-(trifluoromethoxy)benzyl]carbamoyl}-4-{[4-(trifluoromethoxy)phenyl]sulfonyl}piperazin-1-yl]pyridazine-3-carboxamide, ... (4 entities in total)
• 機能のキーワード: ns5b, polymerase, hcv, fingers, palm, thumb, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 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 (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): Q9WMX2
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 131138.07

構造登録者

Sheriff, S. (登録日: 2011-01-24, 公開日: 2011-04-20, 最終更新日: 2023-09-13)

主引用文献

Gentles, R.G.,Sheriff, S.,Beno, B.R.,Wan, C.,Kish, K.,Ding, M.,Zheng, X.,Chupak, L.,Poss, M.A.,Witmer, M.R.,Morin, P.,Wang, Y.K.,Rigat, K.,Lemm, J.,Voss, S.,Liu, M.,Pelosi, L.,Roberts, S.B.,Gao, M.,Kadow, J.F.
Investigation of the mode of binding of a novel series of N-benzyl-4-heteroaryl-1-(phenylsulfonyl)piperazine-2-carboxamides to the hepatitis C virus polymerase.
Bioorg.Med.Chem.Lett., 21:2212-2215, 2011

PubMed Abstract: Structure based rationales for the activities of potent N-benzyl-4-heteroaryl-1-(phenylsulfonyl)piperazine-2-carboxamide inhibitors of the hepatitis C viral polymerase are described herein. These compounds bind to the hepatitis C virus non-structural protein 5B (NS5B), and co-crystal structures of select examples from this series with NS5B are reported. Comparison of co-crystal structures of a potent analog with both NS5B genotype 1a and genotype 1b provides a possible explanation for the genotype-selectivity observed with this compound class and suggests opportunities for the further optimization of the series.

PubMed: 21441029
DOI: 10.1016/j.bmcl.2011.03.011

実験手法

X-RAY DIFFRACTION (3.22 Å)