7MGR

SARS-CoV-2 main protease in complex with nsp8/9 substrate peptide

7MGR の概要

• エントリーDOI: 10.2210/pdb7mgr/pdb
• 分子名称: 3C-like proteinase, ALA-VAL-LYS-LEU-GLN-ASN-ASN-GLU (3 entities in total)
• 機能のキーワード: protease, 3c-like protease, viral protein, hydrolase
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 34822.65

構造登録者

MacDonald, E.A.,Windsor, I.W.,Hinshaw, S.M. (登録日: 2021-04-13, 公開日: 2021-06-23, 最終更新日: 2023-10-18)

主引用文献

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

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: 34437808
DOI: 10.1021/acsinfecdis.1c00237

実験手法

X-RAY DIFFRACTION (1.94 Å)