6W5J

1.85 A resolution structure of Norovirus 3CL protease in complex with inhibitor 7d

6W5J の概要

• エントリーDOI: 10.2210/pdb6w5j/pdb
• 分子名称: 3C-LIKE PROTEASE, 2-(3-chlorophenyl)-2-methylpropyl [(2S)-3-cyclohexyl-1-({(1R,2S)-1-hydroxy-3-[(3S)-2-oxopyrrolidin-3-yl]-1-sulfanylpropan-2-yl}amino)-1-oxopropan-2-yl]carbamate (3 entities in total)
• 機能のキーワード: protease, norovirus 3cl protease, inhibitors, hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Norwalk virus (strain GI/Human/United States/Norwalk/1968) (Hu/NV/NV/1968/US)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 41098.15

構造登録者

Lovell, S.,Kashipathy, M.M.,Battaile, K.P.,Rathnayake, A.D.,Kim, Y.,Chang, K.O.,Groutas, W.C. (登録日: 2020-03-13, 公開日: 2020-09-30, 最終更新日: 2024-11-20)

主引用文献

Rathnayake, A.D.,Kim, Y.,Dampalla, C.S.,Nguyen, H.N.,Jesri, A.M.,Kashipathy, M.M.,Lushington, G.H.,Battaile, K.P.,Lovell, S.,Chang, K.O.,Groutas, W.C.
Structure-Guided Optimization of Dipeptidyl Inhibitors of Norovirus 3CL Protease.
J.Med.Chem., 63:11945-11963, 2020

PubMed Abstract: Acute gastroenteritis caused by noroviruses has a major impact on public health worldwide in terms of morbidity, mortality, and economic burden. The disease impacts most severely immunocompromised patients, the elderly, and children. The current lack of approved vaccines and small-molecule therapeutics for the treatment and prophylaxis of norovirus infections underscores the need for the development of norovirus-specific drugs. The studies described herein entail the use of the -dimethyl moiety as a means of improving the pharmacological activity and physicochemical properties of a dipeptidyl series of transition state inhibitors of norovirus 3CL protease, an enzyme essential for viral replication. Several compounds were found to be potent inhibitors of the enzyme in biochemical and cell-based assays. The pharmacological activity and cellular permeability of the inhibitors were found to be sensitive to the location of the -dimethyl group.

PubMed: 32945669
DOI: 10.1021/acs.jmedchem.0c01252

実験手法

X-RAY DIFFRACTION (1.85 Å)