Surface cysteines could protect the SARS-CoV-2 main protease from oxidative damage
Abstract
The SARS-CoV-2 main protease (Mᵖʳᵒ) is responsible for cleaving twelve nonstructural proteins from the viral polyprotein. Mᵖʳᵒ, a cysteine protease, is characterized by a large number of noncatalytic cysteine (Cys) residues, none involved in disulfide bonds. In the absence of a tertiary-structure stabilizing role for these residues, a possible alternative is that they are involved in redox processes. We report experimental work in support of a proposal that surface cysteines on M^(pro) can protect the active-site Cys145 from oxidation by reactive oxygen species (ROS). In investigations of enzyme kinetics, we found that mutating three surface cysteines to serines did not greatly affect activity, which in turn indicates that these cysteines could protect Cys145 from oxidative damage.
Additional Information
© 2022 Elsevier Inc. Received 2 March 2022, Revised 28 April 2022, Accepted 29 May 2022, Available online 2 June 2022. We thank Dr. Jennifer Keeffe for assistance with SEC-MALS. Experimental work was performed in the Caltech Mass Spectrometry Laboratory in the Division of Chemistry and Chemical Engineering; and the Beckman Institute Laser Resource Center and Proteome Exploration Laboratory supported by the Arnold and Mabel Beckman Foundation. The work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under award number R01DK019038. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. CRediT authorship contribution statement: Raheleh Ravanfar: Investigation, Methodology, Writing – original draft, Writing – review & editing. Yuling Sheng: Investigation. Mona Shahgholi: Investigation, Methodology, Writing – review & editing. Brett Lomenick: Investigation, Methodology, Formal analysis, Writing – review & editing. Jeff Jones: Investigation, Methodology, Formal analysis, Writing – review & editing. Tsui-Fen Chou: Writing – review & editing, Methodology. Harry B. Gray: Funding acquisition, Project administration, Writing – review & editing. Jay R. Winkler: Conceptualization, Funding acquisition, Project administration, Writing – review & editing. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.Attached Files
Published - 1-s2.0-S0162013422001751-main.pdf
Supplemental Material - 1-s2.0-S0162013422001751-mmc1.docx
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Additional details
- PMCID
- PMC9161685
- Eprint ID
- 115017
- Resolver ID
- CaltechAUTHORS:20220603-698843600
- Arnold and Mabel Beckman Foundation
- R01DK019038
- NIH
- Created
-
2022-06-03Created from EPrint's datestamp field
- Updated
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2022-06-30Created from EPrint's last_modified field
- Caltech groups
- COVID-19, Division of Biology and Biological Engineering