7MGS
SARS-CoV-2 main protease in complex with N-terminal autoprocessing substrate
Summary for 7MGS
| Entry DOI | 10.2210/pdb7mgs/pdb |
| Descriptor | 3C-like proteinase, SER-ALA-VAL-LEU-GLN-SER-GLY-PHE, CHLORIDE ION, ... (4 entities in total) |
| Functional Keywords | protease, 3c-like protease, viral protein, hydrolase |
| Biological source | Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2) More |
| Total number of polymer chains | 2 |
| Total formula weight | 34794.02 |
| Authors | MacDonald, E.A.,Windsor, I.W.,Hinshaw, S.M. (deposition date: 2021-04-13, release date: 2021-06-23, Last modification date: 2023-10-18) |
| Primary citation | MacDonald, E.A.,Frey, G.,Namchuk, M.N.,Harrison, S.C.,Hinshaw, S.M.,Windsor, I.W. Recognition of Divergent Viral Substrates by the SARS-CoV-2 Main Protease. Acs Infect Dis., 7:2591-2595, 2021 Cited by PubMed Abstract: The main protease (M) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease (COVID-19), is an ideal target for pharmaceutical inhibition. M is conserved among coronaviruses and distinct from human proteases. Viral replication depends on the cleavage of the viral polyprotein at multiple sites. We present crystal structures of SARS-CoV-2 M bound to two viral substrate peptides. The structures show how M recognizes distinct substrates and how subtle changes in substrate accommodation can drive large changes in catalytic efficiency. One peptide, constituting the junction between viral nonstructural proteins 8 and 9 (nsp8/9), has P1' and P2' residues that are unique among the SARS-CoV-2 M cleavage sites but conserved among homologous junctions in coronaviruses. M cleaves nsp8/9 inefficiently, and amino acid substitutions at P1' or P2' can enhance catalysis. Visualization of M with intact substrates provides new templates for antiviral drug design and suggests that the coronavirus lifecycle selects for finely tuned substrate-dependent catalytic parameters. PubMed: 34437808DOI: 10.1021/acsinfecdis.1c00237 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.84 Å) |
Structure validation
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