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8U1V

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

Summary for 8U1V
Entry DOI10.2210/pdb8u1v/pdb
Related8U1W
DescriptorPeptidase C37 (2 entities in total)
Functional Keywordsprotease, 3-chymotrypsin-like protease, 3cl-pro, viral protein
Biological sourceNorovirus Hu/GII.4/Sydney/NSW0514/2012/AU
Total number of polymer chains4
Total formula weight77321.20
Authors
Eruera, A.R.,Campbell, A.C.,Krause, K.L. (deposition date: 2023-09-03, release date: 2024-01-31)
Primary citationEruera, 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
Cited by
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
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (2.79 Å)
Structure validation

226707

数据于2024-10-30公开中

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