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Structural plasticity of SARS-CoV-2 3CL Mpro active site cavity revealed by room temperature X-ray crystallography

Author

Listed:
  • Daniel W. Kneller

    (Oak Ridge National Laboratory)

  • Gwyndalyn Phillips

    (Oak Ridge National Laboratory)

  • Hugh M. O’Neill

    (Oak Ridge National Laboratory)

  • Robert Jedrzejczak

    (University of Chicago
    Argonne National Laboratory)

  • Lucy Stols

    (University of Chicago)

  • Paul Langan

    (Oak Ridge National Laboratory)

  • Andrzej Joachimiak

    (University of Chicago
    Argonne National Laboratory
    University of Chicago)

  • Leighton Coates

    (Oak Ridge National Laboratory)

  • Andrey Kovalevsky

    (Oak Ridge National Laboratory)

Abstract

The COVID-19 disease caused by the SARS-CoV-2 coronavirus has become a pandemic health crisis. An attractive target for antiviral inhibitors is the main protease 3CL Mpro due to its essential role in processing the polyproteins translated from viral RNA. Here we report the room temperature X-ray structure of unliganded SARS-CoV-2 3CL Mpro, revealing the ligand-free structure of the active site and the conformation of the catalytic site cavity at near-physiological temperature. Comparison with previously reported low-temperature ligand-free and inhibitor-bound structures suggest that the room temperature structure may provide more relevant information at physiological temperatures for aiding in molecular docking studies.

Suggested Citation

  • Daniel W. Kneller & Gwyndalyn Phillips & Hugh M. O’Neill & Robert Jedrzejczak & Lucy Stols & Paul Langan & Andrzej Joachimiak & Leighton Coates & Andrey Kovalevsky, 2020. "Structural plasticity of SARS-CoV-2 3CL Mpro active site cavity revealed by room temperature X-ray crystallography," Nature Communications, Nature, vol. 11(1), pages 1-6, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16954-7
    DOI: 10.1038/s41467-020-16954-7
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    Cited by:

    1. Jaeyong Lee & Calem Kenward & Liam J. Worrall & Marija Vuckovic & Francesco Gentile & Anh-Tien Ton & Myles Ng & Artem Cherkasov & Natalie C. J. Strynadka & Mark Paetzel, 2022. "X-ray crystallographic characterization of the SARS-CoV-2 main protease polyprotein cleavage sites essential for viral processing and maturation," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    2. Mikhail A. Hameedi & Erica T. Prates & Michael R. Garvin & Irimpan I. Mathews & B. Kirtley Amos & Omar Demerdash & Mark Bechthold & Mamta Iyer & Simin Rahighi & Daniel W. Kneller & Andrey Kovalevsky &, 2022. "Structural and functional characterization of NEMO cleavage by SARS-CoV-2 3CLpro," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    3. Daniel W. Kneller & Hui Li & Gwyndalyn Phillips & Kevin L. Weiss & Qiu Zhang & Mark A. Arnould & Colleen B. Jonsson & Surekha Surendranathan & Jyothi Parvathareddy & Matthew P. Blakeley & Leighton Coa, 2022. "Covalent narlaprevir- and boceprevir-derived hybrid inhibitors of SARS-CoV-2 main protease," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    4. Gabriela Dias Noske & Yun Song & Rafaela Sachetto Fernandes & Rod Chalk & Haitem Elmassoudi & Lizbé Koekemoer & C. David Owen & Tarick J. El-Baba & Carol V. Robinson & Glaucius Oliva & Andre Schutzer , 2023. "An in-solution snapshot of SARS-COV-2 main protease maturation process and inhibition," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    5. Ala M. Shaqra & Sarah N. Zvornicanin & Qiu Yu J. Huang & Gordon J. Lockbaum & Mark Knapp & Laura Tandeske & David T. Bakan & Julia Flynn & Daniel N. A. Bolon & Stephanie Moquin & Dustin Dovala & Nese , 2022. "Defining the substrate envelope of SARS-CoV-2 main protease to predict and avoid drug resistance," Nature Communications, Nature, vol. 13(1), pages 1-11, December.

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