7JIW

The crystal structure of Papain-Like Protease of SARS CoV-2 in complex with PLP_Snyder530 inhibitor

7JIW の概要

• エントリーDOI: 10.2210/pdb7jiw/pdb
• 関連するPDBエントリー: 6WRH 6WZU 7JIR 7JIT 7JIV
• 分子名称: Papain-like protease, 5-(acryloylamino)-2-methyl-N-[(1R)-1-(naphthalen-1-yl)ethyl]benzamide, ZINC ION, ... (6 entities in total)
• 機能のキーワード: 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
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 36900.88

構造登録者

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) (登録日: 2020-07-23, 公開日: 2020-08-05, 最終更新日: 2023-10-18)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.3 Å)