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A Crystallographic ...
A Crystallographic Snapshot of SARS-CoV-2 Main Protease Maturation Process : SARS-CoV-2 Mpro maturation
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- Noske, G. D. (author)
- University of São Paulo
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- Nakamura, A. M. (author)
- University of São Paulo
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- Gawriljuk, V. O. (author)
- University of São Paulo
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- Fernandes, R. S. (author)
- University of São Paulo
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- Lima, G. M.A. (author)
- Lund University,Lunds universitet,MAX IV-laboratoriet,MAX IV Laboratory
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- Rosa, H. V.D. (author)
- University of São Paulo
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- Pereira, H. D. (author)
- University of São Paulo
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- Zeri, A. C.M. (author)
- Brazilian Center For Research In Energy And Materials (CNPEM)
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- Nascimento, A. F.Z. (author)
- Brazilian Center For Research In Energy And Materials (CNPEM)
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- Freire, M. C.L.C. (author)
- University of São Paulo
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- Fearon, D. (author)
- Diamond Light Source
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- Douangamath, A. (author)
- Diamond Light Source
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- von Delft, F. (author)
- University of Oxford,University of Johannesburg,Diamond Light Source
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- Oliva, G. (author)
- University of São Paulo
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- Godoy, A. S. (author)
- University of São Paulo
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(creator_code:org_t)
- Elsevier BV, 2021
- 2021
- English.
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In: Journal of Molecular Biology. - : Elsevier BV. - 0022-2836. ; 433:18
- Related links:
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http://dx.doi.org/10...
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https://doi.org/10.1...
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https://doi.org/10.1...
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Abstract
Subject headings
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- 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.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Keyword
- COVID
- drug discovery
- M
- maturation
- SARS-CoV-2
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Noske, G. D.
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Nakamura, A. M.
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Gawriljuk, V. O.
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Fernandes, R. S.
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Lima, G. M.A.
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Rosa, H. V.D.
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show more...
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Pereira, H. D.
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Zeri, A. C.M.
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Nascimento, A. F ...
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Freire, M. C.L.C ...
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Fearon, D.
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Douangamath, A.
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von Delft, F.
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Oliva, G.
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Godoy, A. S.
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show less...
- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biochemistry and ...
- Articles in the publication
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Journal of Molec ...
- By the university
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Lund University