7T2V

SARS CoV2 Mpro C145S mutant

Summary for 7T2V

• Entry DOI: 10.2210/pdb7t2v/pdb
• Descriptor: 3C-Like Protease (2 entities in total)
• Functional Keywords: sars-cov2 2c-like protease, mpro, 2clpro, c145s mutation, hydrolase
• Biological source: Severe acute respiratory syndrome coronavirus 2
• Total number of polymer chains: 4
• Total formula weight: 142257.58

Authors

Mathews, I.I.,Hameedi, M.A.,Wakatsuki, S. (deposition date: 2021-12-06, release date: 2022-09-14, Last modification date: 2024-04-03)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.47 Å)