7DVW

SARS-CoV-2 Mpro mutant (H41A) in complex with nsp5|6 peptidyl substrate

7DVW の概要

• エントリーDOI: 10.2210/pdb7dvw/pdb
• 分子名称: 3C-like proteinase, nsp5/6 peptidyl substrate, DIMETHYL SULFOXIDE, ... (4 entities in total)
• 機能のキーワード: protease, viral protein
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 36007.15

構造登録者

Liu, X.,Zhao, Y.,Yang, H.,Rao, Z. (登録日: 2021-01-15, 公開日: 2022-01-19, 最終更新日: 2023-11-29)

主引用文献

Zhao, Y.,Zhu, Y.,Liu, X.,Jin, Z.,Duan, Y.,Zhang, Q.,Wu, C.,Feng, L.,Du, X.,Zhao, J.,Shao, M.,Zhang, B.,Yang, X.,Wu, L.,Ji, X.,Guddat, L.W.,Yang, K.,Rao, Z.,Yang, H.
Structural basis for replicase polyprotein cleavage and substrate specificity of main protease from SARS-CoV-2.
Proc.Natl.Acad.Sci.USA, 119:e2117142119-e2117142119, 2022

PubMed Abstract: The main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a key enzyme, which extensively digests CoV replicase polyproteins essential for viral replication and transcription, making it an attractive target for antiviral drug development. However, the molecular mechanism of how Mpro of SARS-CoV-2 digests replicase polyproteins, releasing the nonstructural proteins (nsps), and its substrate specificity remain largely unknown. Here, we determine the high-resolution structures of SARS-CoV-2 Mpro in its resting state, precleavage state, and postcleavage state, constituting a full cycle of substrate cleavage. The structures show the delicate conformational changes that occur during polyprotein processing. Further, we solve the structures of the SARS-CoV-2 Mpro mutant (H41A) in complex with six native cleavage substrates from replicase polyproteins, and demonstrate that SARS-CoV-2 Mpro can recognize sequences as long as 10 residues but only have special selectivity for four subsites. These structural data provide a basis to develop potent new inhibitors against SARS-CoV-2.

PubMed: 35380892
DOI: 10.1073/pnas.2117142119

実験手法

X-RAY DIFFRACTION (1.49 Å)