7UU9

Crystal structure of the SARS-CoV-2 main protease in its apo-form

7UU9 の概要

• エントリーDOI: 10.2210/pdb7uu9/pdb
• 分子名称: 3C-like proteinase nsp5 (2 entities in total)
• 機能のキーワード: main protease, viral protein, hydrolase
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 33873.55

構造登録者

Yang, K.S.,Liu, W.R. (登録日: 2022-04-28, 公開日: 2023-01-25, 最終更新日: 2024-10-09)

主引用文献

Yang, K.S.,Blankenship, L.R.,Kuo, S.A.,Sheng, Y.J.,Li, P.,Fierke, C.A.,Russell, D.H.,Yan, X.,Xu, S.,Liu, W.R.
A Novel Y-Shaped, S-O-N-O-S-Bridged Cross-Link between Three Residues C22, C44, and K61 Is Frequently Observed in the SARS-CoV-2 Main Protease.
Acs Chem.Biol., 18:449-455, 2023

PubMed Abstract: As the COVID-19 pathogen, SARS-CoV-2 relies on its main protease (M) for pathogenesis and replication. During crystallographic analyses of M crystals that were exposed to the air, a uniquely Y-shaped, S-O-N-O-S-bridged post-translational cross-link that connects three residues C22, C44, and K61 at their side chains was frequently observed. As a novel covalent modification, this cross-link serves potentially as a redox switch to regulate the catalytic activity of M, a demonstrated drug target of COVID-19. The formation of this linkage leads to a much more open active site that can potentially be targeted for the development of novel SARS-CoV-2 antivirals. The structural rearrangement of M by this cross-link indicates that small molecules that lock M in the cross-linked form can potentially be used with other active-site-targeting molecules such as paxlovid for synergistic effects in inhibiting SARS-CoV-2 viral replication.

PubMed: 36629751
DOI: 10.1021/acschembio.2c00695

実験手法

X-RAY DIFFRACTION (2.47 Å)