7KVL

SARS-CoV-2 Main protease immature form - FMAX Library E01 fragment

7KVL の概要

• エントリーDOI: 10.2210/pdb7kvl/pdb
• 分子名称: 3C-like proteinase, DI(HYDROXYETHYL)ETHER, 2-chloropyridine-4-carboxamide, ... (6 entities in total)
• 機能のキーワード: mpro, main protease, covid-19, sars-cov-2, 3cl, hydrolase
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 70223.79

構造登録者

Noske, G.D.,Nakamura, A.M.,Gawriljuk, V.O.,Lima, G.M.A.,Zeri, A.C.M.,Nascimento, A.F.Z.,Fernandes, R.S.,Oliva, G.,Godoy, A.S. (登録日: 2020-11-28, 公開日: 2020-12-09, 最終更新日: 2023-10-18)

主引用文献

Noske, G.D.,Nakamura, A.M.,Gawriljuk, V.O.,Fernandes, R.S.,Lima, G.M.A.,Rosa, H.V.D.,Pereira, H.D.,Zeri, A.C.M.,Nascimento, A.F.Z.,Freire, M.C.L.C.,Fearon, D.,Douangamath, A.,von Delft, F.,Oliva, G.,Godoy, A.S.
A Crystallographic Snapshot of SARS-CoV-2 Main Protease Maturation Process.
J.Mol.Biol., 433:167118-167118, 2021

PubMed Abstract: SARS-CoV-2 is the causative agent of COVID-19. The dimeric form of the viral M is responsible for the cleavage of the viral polyprotein in 11 sites, including its own N and C-terminus. The lack of structural information for intermediary forms of M is a setback for the understanding its self-maturation process. Herein, we used X-ray crystallography combined with biochemical data to characterize multiple forms of SARS-CoV-2 M. For the immature form, we show that extra N-terminal residues caused conformational changes in the positioning of domain-three over the active site, hampering the dimerization and diminishing its activity. We propose that this form preludes the cis and trans-cleavage of N-terminal residues. Using fragment screening, we probe new cavities in this form which can be used to guide therapeutic development. Furthermore, we characterized a serine site-directed mutant of the M bound to its endogenous N and C-terminal residues during dimeric association stage of the maturation process. We suggest this form is a transitional state during the C-terminal trans-cleavage. This data sheds light in the structural modifications of the SARS-CoV-2 main protease during its self-maturation process.

PubMed: 34174328
DOI: 10.1016/j.jmb.2021.167118

実験手法

X-RAY DIFFRACTION (2.09 Å)