8U1V

Structure of Norovirus (Hu/GII.4/Sydney/NSW0514/2012/AU) protease in the ligand-free state

8U1V の概要

• エントリーDOI: 10.2210/pdb8u1v/pdb
• 関連するPDBエントリー: 8U1W
• 分子名称: Peptidase C37 (2 entities in total)
• 機能のキーワード: protease, 3-chymotrypsin-like protease, 3cl-pro, viral protein
• 由来する生物種: Norovirus Hu/GII.4/Sydney/NSW0514/2012/AU
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 77321.20

構造登録者

Eruera, A.R.,Campbell, A.C.,Krause, K.L. (登録日: 2023-09-03, 公開日: 2024-01-31)

主引用文献

Eruera, A.R.,McSweeney, A.M.,McKenzie-Goldsmith, G.M.,Opel-Reading, H.K.,Thomas, S.X.,Campbell, A.C.,Stubbing, L.,Siow, A.,Hubert, J.G.,Brimble, M.A.,Ward, V.K.,Krause, K.L.
Crystal Structure of Inhibitor-Bound GII.4 Sydney 2012 Norovirus 3C-Like Protease.
Viruses, 15:-, 2023

PubMed Abstract: Norovirus is the leading cause of viral gastroenteritis worldwide, and there are no approved vaccines or therapeutic treatments for chronic or severe norovirus infections. The structural characterisation of the norovirus protease and drug development has predominantly focused upon GI.1 noroviruses, despite most global outbreaks being caused by GII.4 noroviruses. Here, we determined the crystal structures of the GII.4 Sydney 2012 ligand-free norovirus protease at 2.79 Å and at 1.83 Å with a covalently bound high-affinity (IC = 0.37 µM) protease inhibitor (NV-004). We show that the active sites of the ligand-free protease structure are present in both open and closed conformations, as determined by their Arg112 side chain orientation. A comparative analysis of the ligand-free and ligand-bound protease structures reveals significant structural differences in the active site cleft and substrate-binding pockets when an inhibitor is covalently bound. We also report a second molecule of NV-004 non-covalently bound within the S4 substrate binding pocket via hydrophobic contacts and a water-mediated hydrogen bond. These new insights can guide structure-aided drug design against the GII.4 genogroup of noroviruses.

PubMed: 38005879
DOI: 10.3390/v15112202

実験手法

X-RAY DIFFRACTION (2.79 Å)