7JIR

The crystal structure of Papain-Like Protease of SARS CoV-2 , C111S mutant, in complex with PLP_Snyder457 inhibitor

Summary for 7JIR

• Entry DOI: 10.2210/pdb7jir/pdb
• Related: 6WRH 6WZU
• Descriptor: Papain-like protease, 5-amino-2-methyl-N-[(1R)-1-naphthalen-1-ylethyl]benzamide, ZINC ION, ... (7 entities in total)
• Functional Keywords: covid-19, coronavirus, sars, cov-2, papain-like protease, idp51000, center for structural genomics of infectious diseases, csgid, hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV)
• Total number of polymer chains: 1
• Total formula weight: 36889.81

Authors

Osipiuk, J.,Tesar, C.,Endres, M.,Lisnyak, V.,Maki, S.,Taylor, C.,Zhang, Y.,Zhou, Z.,Azizi, S.A.,Jones, K.,Kathayat, R.,Snyder, S.A.,Dickinson, B.C.,Joachimiak, A.,Center for Structural Genomics of Infectious Diseases (CSGID) (deposition date: 2020-07-23, release date: 2020-08-05, Last modification date: 2023-10-18)

Primary citation

Osipiuk, J.,Azizi, S.A.,Dvorkin, S.,Endres, M.,Jedrzejczak, R.,Jones, K.A.,Kang, S.,Kathayat, R.S.,Kim, Y.,Lisnyak, V.G.,Maki, S.L.,Nicolaescu, V.,Taylor, C.A.,Tesar, C.,Zhang, Y.A.,Zhou, Z.,Randall, G.,Michalska, K.,Snyder, S.A.,Dickinson, B.C.,Joachimiak, A.
Structure of papain-like protease from SARS-CoV-2 and its complexes with non-covalent inhibitors.
Nat Commun, 12:743-743, 2021

PubMed Abstract: The pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continues to expand. Papain-like protease (PLpro) is one of two SARS-CoV-2 proteases potentially targetable with antivirals. PLpro is an attractive target because it plays an essential role in cleavage and maturation of viral polyproteins, assembly of the replicase-transcriptase complex, and disruption of host responses. We report a substantive body of structural, biochemical, and virus replication studies that identify several inhibitors of the SARS-CoV-2 enzyme. We determined the high resolution structure of wild-type PLpro, the active site C111S mutant, and their complexes with inhibitors. This collection of structures details inhibitors recognition and interactions providing fundamental molecular and mechanistic insight into PLpro. All compounds inhibit the peptidase activity of PLpro in vitro, some block SARS-CoV-2 replication in cell culture assays. These findings will accelerate structure-based drug design efforts targeting PLpro to identify high-affinity inhibitors of clinical value.

PubMed: 33531496
DOI: 10.1038/s41467-021-21060-3

Experimental method

X-RAY DIFFRACTION (2.09 Å)