5DGJ

1.0A resolution structure of Norovirus 3CL protease in complex an oxadiazole-based, cell permeable macrocyclic (20-mer) inhibitor

5DGJ の概要

• エントリーDOI: 10.2210/pdb5dgj/pdb
• 関連するPDBエントリー: 5DG6
• 関連するBIRD辞書のPRD_ID: PRD_002189
• 分子名称: 3C-LIKE PROTEASE, tert-butyl [(4S,7S,10S)-7-(cyclohexylmethyl)-10-(hydroxymethyl)-5,8,13-trioxo-22-oxa-6,9,14,20,21-pentaazabicyclo[17.2.1]docosa-1(21),19-dien-4-yl]carbamate (3 entities in total)
• 機能のキーワード: protease, norovirus, norwalk virus, antiviral inhibitors, oxadiazole inhibitor, cell permeable, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Norwalk virus (Hu/NV/NV/1968/US)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 20718.86

構造登録者

Lovell, S.,Battaile, K.P.,Mehzabeen, N.,Damalanka, V.C.,Kim, Y.,Alliston, K.R.,Weerawarna, P.M.,Kankanamalage, A.C.G.,Lushington, G.H.,Chang, K.-O.,Groutas, W.C. (登録日: 2015-08-27, 公開日: 2016-02-10, 最終更新日: 2024-11-20)

主引用文献

Damalanka, V.C.,Kim, Y.,Alliston, K.R.,Weerawarna, P.M.,Galasiti Kankanamalage, A.C.,Lushington, G.H.,Mehzabeen, N.,Battaile, K.P.,Lovell, S.,Chang, K.O.,Groutas, W.C.
Oxadiazole-Based Cell Permeable Macrocyclic Transition State Inhibitors of Norovirus 3CL Protease.
J.Med.Chem., 59:1899-1913, 2016

PubMed Abstract: Human noroviruses are the primary causative agents of acute gastroenteritis and a pressing public health burden worldwide. There are currently no vaccines or small molecule therapeutics available for the treatment or prophylaxis of norovirus infections. Norovirus 3CL protease plays a vital role in viral replication by generating structural and nonstructural proteins via the cleavage of the viral polyprotein. Thus, molecules that inhibit the viral protease may have potential therapeutic value. We describe herein the structure-based design, synthesis, and in vitro and cell-based evaluation of the first class of oxadiazole-based, permeable macrocyclic inhibitors of norovirus 3CL protease.

PubMed: 26823007
DOI: 10.1021/acs.jmedchem.5b01464

実験手法

X-RAY DIFFRACTION (1 Å)