%0 Journal Article
%A Reinke, Patrick
%A Schubert, Robin
%A Oberthür, Dominik
%A Galchenkova, Marina
%A Rahmani Mashhour, Aida
%A Guenther, Sebastian
%A Chretien, Anaïs
%A Round, Adam
%A Seychell, Brandon Charles
%A Norton-Baker, Brenna
%A Kim, Chan
%A Schmidt, Christina
%A Koua, Faisal H. M.
%A Tolstikova, Alexandra
%A Ewert, Wiebke
%A Pena Murillo, Gisel Esperanza
%A Mills, Grant
%A Kirkwood, Henry
%A Brognaro, Hévila
%A Han, Huijong
%A Koliyadu, Jayanath
%A Schulz, Joachim
%A Bielecki, Johan
%A Lieske, Julia
%A Maracke, Julia
%A Knoska, Juraj
%A Lorenzen, Kristina
%A Brings, Lea
%A Sikorski, Marcin
%A Kloos, Marco
%A Vakili, Mohammad
%A Vagovic, Patrik
%A Middendorf, Philipp
%A de Wijn, Raphael
%A Bean, Richard
%A Letrun, Romain
%A Han, Seonghyun
%A Falke, Sven
%A Geng, Tian
%A Sato, Tokushi
%A Srinivasan, Vasundara
%A Kim, Yoonhee
%A Yefanov, Oleksandr M.
%A Gelisio, Luca
%A Beck, Tobias
%A Doré, Andrew S.
%A Mancuso, Adrian P.
%A Betzel, Christian
%A Bajt, Saša
%A Redecke, Lars
%A Chapman, Henry N.
%A Meents, Alke
%A Turk, Dušan
%A Hinrichs, Winfried
%A Lane, Thomas
%T SARS-CoV-2 Mpro responds to oxidation by forming disulfide and NOS/SONOS bonds
%J Nature Communications
%V 15
%N 1
%@ 2041-1723
%C [London]
%I Nature Publishing Group UK
%M PUBDB-2023-05575
%P 3827
%D 2024
%X 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:38714735
%U <Go to ISI:>//WOS:001215774800049
%R 10.1038/s41467-024-48109-3
%U https://bib-pubdb1.desy.de/record/593910