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Nat Commun . Structural Plasticity of SARS-CoV-2 3CL M pro Active Site Cavity Revealed by Room Temperature X-ray Crystallography

tetano

Editor, Senior Moderator
Nat Commun


. 2020 Jun 24;11(1):3202.
doi: 10.1038/s41467-020-16954-7.
Structural Plasticity of SARS-CoV-2 3CL M [SUP]pro[/SUP] Active Site Cavity Revealed by Room Temperature X-ray Crystallography


Daniel W Kneller[SUP] 1 [/SUP], Gwyndalyn Phillips[SUP] 1 [/SUP], Hugh M O'Neill[SUP] 1 [/SUP], Robert Jedrzejczak[SUP] 2 3 [/SUP], Lucy Stols[SUP] 2 [/SUP], Paul Langan[SUP] 1 [/SUP], Andrzej Joachimiak[SUP] 2 3 4 [/SUP], Leighton Coates[SUP] 5 [/SUP], Andrey Kovalevsky[SUP] 6 [/SUP]



Affiliations

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 M[SUP]pro[/SUP] 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 M[SUP]pro[/SUP], 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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