5TG2

1.75 A resolution structure of Norovirus 3CL protease in complex with the a n-pentyl substituted macrocyclic inhibitor (17-mer)

Summary for 5TG2

• Entry DOI: 10.2210/pdb5tg2/pdb
• Related: 5TG1
• Related PRD ID: PRD_002248
• Descriptor: 3C-LIKE PROTEASE, (4S,7S,17R)-7-(hydroxymethyl)-4-(2-methylpropyl)-17-pentyl-1-oxa-3,6,11-triazacycloheptadecane-2,5,10-trione (3 entities in total)
• Functional Keywords: protease, norovirus, norwalk virus, antiviral inhibitors, macrocyclic inhibitor, hydrolase-hydrolase inhibitor complex, protease-protease inhibitor complex, protease/protease inhibitor
• Biological source: Norwalk virus (Hu/NV/NV/1968/US)
• Total number of polymer chains: 1
• Total formula weight: 20567.74

Authors

Lovell, S.,Battaile, K.P.,Mehzabeen, N.,Damalanka, V.C.,Kim, Y.,Kankanamalage, A.C.G.,Chang, K.-O.,Groutas, W.C. (deposition date: 2016-09-27, release date: 2017-01-11, Last modification date: 2024-11-20)

Primary citation

Damalanka, V.C.,Kim, Y.,Galasiti Kankanamalage, A.C.,Lushington, G.H.,Mehzabeen, N.,Battaile, K.P.,Lovell, S.,Chang, K.O.,Groutas, W.C.
Design, synthesis, and evaluation of a novel series of macrocyclic inhibitors of norovirus 3CL protease.
Eur J Med Chem, 127:41-61, 2016

PubMed Abstract: Norovirus infections have a major impact on public health worldwide, yet there is a current dearth of norovirus-specific therapeutics and prophylactics. This report describes the discovery of a novel class of macrocyclic inhibitors of norovirus 3C-like protease, a cysteine protease that is essential for virus replication. SAR, structural, and biochemical studies were carried out to ascertain the effect of structure on pharmacological activity and permeability. Insights gained from these studies have laid a solid foundation for capitalizing on the therapeutic potential of the series of inhibitors described herein.

PubMed: 28038326
DOI: 10.1016/j.ejmech.2016.12.033

Experimental method

X-RAY DIFFRACTION (1.75 Å)