3Q0Z

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

3Q0Z の概要

• エントリーDOI: 10.2210/pdb3q0z/pdb
• 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, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: ns5b, polymerase, hcv, fingers, palm, thumb, transferase, 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: 130145.13

構造登録者

Sheriff, S. (登録日: 2010-12-16, 公開日: 2011-04-27, 最終更新日: 2023-09-13)

主引用文献

Zheng, X.,Hudyma, T.W.,Martin, S.W.,Bergstrom, C.,Ding, M.,He, F.,Romine, J.,Poss, M.A.,Kadow, J.F.,Chang, C.H.,Wan, J.,Witmer, M.R.,Morin, P.,Camac, D.M.,Sheriff, S.,Beno, B.R.,Rigat, K.L.,Wang, Y.K.,Fridell, R.,Lemm, J.,Qiu, D.,Liu, M.,Voss, S.,Pelosi, L.,Roberts, S.B.,Gao, M.,Knipe, J.,Gentles, R.G.
Syntheses and initial evaluation of a series of indolo-fused heterocyclic inhibitors of the polymerase enzyme (NS5B) of the hepatitis C virus.
Bioorg.Med.Chem.Lett., 21:2925-2929, 2011

PubMed Abstract: Herein, we present initial SAR studies on a series of bridged 2-arylindole-based NS5B inhibitors. The introduction of bridging elements between the indole N1 and the ortho-position of the 2-aryl moiety resulted in conformationally constrained heterocycles that possess multiple additional vectors for further exploration. The binding mode and pharmacokinetic (PK) properties of select examples, including: 13-cyclohexyl-6-oxo-6,7-dihydro-5H-indolo[2,1-d][1,4]benzodiazepine-10-carboxylic acid (7) (IC(50)=0.07 μM, %F=18), are reported.

PubMed: 21486696
DOI: 10.1016/j.bmcl.2011.03.067

実験手法

X-RAY DIFFRACTION (2.29 Å)