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A Novel Y-Shaped, S-O-N-O-S-Bridged Crosslink between Three Residues C22, C44, and K61 Is Frequently Observed in the SARS-CoV-2 Main Protease

ACS Chemical Biology. 2024-07; 
Kai S. Yang; Lauren R. Blankenship; Syuan-Ting Alex Kuo; Yan J. Sheng; Pingwei Li; Carol A. Fierke; David H. Russell; Xin Yan; Shiqing Xu; Wenshe Ray Liu
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Protein and Antibody Isolation cells were harvested and lysed in buffer A (20 mM Tris, 100 mM NaCl, 10 mM imidazole, pH 8.0). The supernatant was loaded onto a nickel-chelating column (GenScript) washed with buffer A, followed by elution with buffer B (20 mM Tris, 100 mM NaCl, 250 mM imidazole, pH 8.0). The eluted protein solution was desalted Get A Quote

摘要

As the COVID-19 pathogen, SARS-CoV-2 relies on its main protease (M Pro ) for pathogenesis and replication. During the crystallographic analyses of M Pro crystals that were exposed to the air, a uniquely Y-shaped, S-O-N-O-S-bridged posttranslational crosslink that connects three residues C22, C44, and K61 at their side chains was frequently observed. As a novel covalent modification, this crosslink serves potentially as a redox switch to regulate the catalytic activity of M Pro , a demonstrated drug target of COVID-19. The formation of this linkage leads to a much more opened active site that can be potentially targeted for the development of novel SARS-CoV-2 antivirals. The structural rearrangement of M Pro by... More

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