TY  - JOUR
AU  - Reinke, Patrick
AU  - Schubert, Robin
AU  - Oberthür, Dominik
AU  - Galchenkova, Marina
AU  - Rahmani Mashhour, Aida
AU  - Guenther, Sebastian
AU  - Chretien, Anaïs
AU  - Round, Adam
AU  - Seychell, Brandon Charles
AU  - Norton-Baker, Brenna
AU  - Kim, Chan
AU  - Schmidt, Christina
AU  - Koua, Faisal H. M.
AU  - Tolstikova, Alexandra
AU  - Ewert, Wiebke
AU  - Pena Murillo, Gisel Esperanza
AU  - Mills, Grant
AU  - Kirkwood, Henry
AU  - Brognaro, Hévila
AU  - Han, Huijong
AU  - Koliyadu, Jayanath
AU  - Schulz, Joachim
AU  - Bielecki, Johan
AU  - Lieske, Julia
AU  - Maracke, Julia
AU  - Knoska, Juraj
AU  - Lorenzen, Kristina
AU  - Brings, Lea
AU  - Sikorski, Marcin
AU  - Kloos, Marco
AU  - Vakili, Mohammad
AU  - Vagovic, Patrik
AU  - Middendorf, Philipp
AU  - de Wijn, Raphael
AU  - Bean, Richard
AU  - Letrun, Romain
AU  - Han, Seonghyun
AU  - Falke, Sven
AU  - Geng, Tian
AU  - Sato, Tokushi
AU  - Srinivasan, Vasundara
AU  - Kim, Yoonhee
AU  - Yefanov, Oleksandr M.
AU  - Gelisio, Luca
AU  - Beck, Tobias
AU  - Doré, Andrew S.
AU  - Mancuso, Adrian P.
AU  - Betzel, Christian
AU  - Bajt, Saša
AU  - Redecke, Lars
AU  - Chapman, Henry N.
AU  - Meents, Alke
AU  - Turk, Dušan
AU  - Hinrichs, Winfried
AU  - Lane, Thomas
TI  - SARS-CoV-2 Mpro responds to oxidation by forming disulfide and NOS/SONOS bonds
JO  - Nature Communications
VL  - 15
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Nature Publishing Group UK
M1  - PUBDB-2023-05575
SP  - 3827
PY  - 2024
AB  - The main protease (M<sup>pro</sup>) of SARS-CoV-2 is critical for viral function and a key drug target. Mpro is only active when reduced; turnover ceases upon oxidation but is restored by re-reduction. This suggests the system has evolved to survive periods in an oxidative environment, but the mechanism of this protection has not been confirmed. Here, we report a crystal structure of oxidized M<sup>pro</sup> showing a disulfide bond between the active site cysteine, C145, and a distal cysteine, C117. Previous work proposed this disulfide provides the mechanism of protection from irreversible oxidation. M<sup>pro</sup> forms an obligate homodimer, and the C117-C145 structure shows disruption of interactions bridging the dimer interface, implying a correlation between oxidation and dimerization. We confirm dimer stability is weakened in solution upon oxidation. Finally, we observe the protein’s crystallization behavior is linked to its redox state. Oxidized M<sup>pro</sup> spontaneously forms a distinct, more loosely packed lattice. Seeding with crystals of this lattice yields a structure with an oxidation pattern incorporating one cysteine-lysine-cysteine (SONOS) and two lysine-cysteine (NOS) bridges. These structures further our understanding of the oxidative regulation of M<sup>pro</sup> and the crystallization conditions necessary to study this structurally.
LB  - PUB:(DE-HGF)16
C6  - pmid:38714735
UR  - <Go to ISI:>//WOS:001215774800049
DO  - DOI:10.1038/s41467-024-48109-3
UR  - https://bib-pubdb1.desy.de/record/593910
ER  -