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

Nature Communications
Daniel W KnellerAndrey Kovalevsky

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.

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Citations

Sep 2, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Kenichi Akaji, Hiroyuki Konno
Oct 3, 2020·Acta Crystallographica. Section F, Structural Biology Communications·Daniel W KnellerLeighton Coates
Dec 15, 2020·Wellcome Open Research·Stefan BressonDavid Tollervey
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Dec 1, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Xiao-Huan LiuTao Wang
Oct 17, 2020·The Journal of Biological Chemistry·Daniel W KnellerAndrey Kovalevsky
Jan 22, 2021·Communications Biology·Vicky ModyShashidharamurthy Taval
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Methods Mentioned

BETA
X-ray
PCR

Software Mentioned

COOT
GROMACS
Molprobity
Molrep
Aimless
Phenix
CrysAlis Pro
CCP4

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