7T2V

SARS CoV2 Mpro C145S mutant

7T2V の概要

• エントリーDOI: 10.2210/pdb7t2v/pdb
• 分子名称: 3C-Like Protease (2 entities in total)
• 機能のキーワード: sars-cov2 2c-like protease, mpro, 2clpro, c145s mutation, hydrolase
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 142257.58

構造登録者

Mathews, I.I.,Hameedi, M.A.,Wakatsuki, S. (登録日: 2021-12-06, 公開日: 2022-09-14, 最終更新日: 2024-04-03)

主引用文献

Hameedi, M.A.,T Prates, E.,Garvin, M.R.,Mathews, I.I.,Amos, B.K.,Demerdash, O.,Bechthold, M.,Iyer, M.,Rahighi, S.,Kneller, D.W.,Kovalevsky, A.,Irle, S.,Vuong, V.Q.,Mitchell, J.C.,Labbe, A.,Galanie, S.,Wakatsuki, S.,Jacobson, D.
Structural and functional characterization of NEMO cleavage by SARS-CoV-2 3CLpro.
Nat Commun, 13:5285-5285, 2022

PubMed Abstract: In addition to its essential role in viral polyprotein processing, the SARS-CoV-2 3C-like protease (3CLpro) can cleave human immune signaling proteins, like NF-κB Essential Modulator (NEMO) and deregulate the host immune response. Here, in vitro assays show that SARS-CoV-2 3CLpro cleaves NEMO with fine-tuned efficiency. Analysis of the 2.50 Å resolution crystal structure of 3CLpro C145S bound to NEMO reveals subsites that tolerate a range of viral and host substrates through main chain hydrogen bonds while also enforcing specificity using side chain hydrogen bonds and hydrophobic contacts. Machine learning- and physics-based computational methods predict that variation in key binding residues of 3CLpro-NEMO helps explain the high fitness of SARS-CoV-2 in humans. We posit that cleavage of NEMO is an important piece of information to be accounted for, in the pathology of COVID-19.

PubMed: 36075915
DOI: 10.1038/s41467-022-32922-9

実験手法

X-RAY DIFFRACTION (2.47 Å)