A Crystallographic Snapshot of SARS-CoV-2 Main Protease Maturation Process : SARS-CoV-2 Mpro maturation

Lima, G. M.A. (författare): Lund University,Lunds universitet,MAX IV-laboratoriet,MAX IV Laboratory

Zeri, A. C.M. (författare): Brazilian Center For Research In Energy And Materials (CNPEM)

Nascimento, A. F.Z. (författare): Brazilian Center For Research In Energy And Materials (CNPEM)

von Delft, F. (författare): Diamond Light Source,University of Oxford,University of Johannesburg

(creator_code:org_t)

Elsevier BV, 2021
2021
Engelska.
Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 0022-2836. ; 433:18

Relaterad länk:: http://dx.doi.org/10...; visa fler...; https://doi.org/10.1...; https://lup.lub.lu.s...; https://doi.org/10.1...; visa färre...

Abstract Ämnesord

Stäng

SARS-CoV-2 is the causative agent of COVID-19. The dimeric form of the viral Mpro 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 Mpro 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 Mpro. 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 Mpro 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.

Av författaren/redakt...: Noske, G. D.; Nakamura, A. M.; Gawriljuk, V. O.; Fernandes, R. S.; Lima, G. M.A.; Rosa, H. V.D.; visa fler...; Pereira, H. D.; Zeri, A. C.M.; Nascimento, A. F ...; Freire, M. C.L.C ...; Fearon, D.; Douangamath, A.; von Delft, F.; Oliva, G.; Godoy, A. S.; visa färre...

Om ämnet

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.