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

Nat Commun. 2020 Jun 24;11(1):3202. doi: 10.1038/s41467-020-16954-7.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Betacoronavirus / enzymology*
  • Catalytic Domain
  • Crystallography, X-Ray
  • Cysteine Endopeptidases / chemistry*
  • Cysteine Endopeptidases / metabolism
  • Cysteine Proteinase Inhibitors / metabolism
  • Ligands
  • Models, Molecular
  • Molecular Dynamics Simulation
  • Protein Binding
  • Protein Conformation
  • Protein Domains
  • Protein Structure, Secondary
  • Temperature
  • Viral Nonstructural Proteins / antagonists & inhibitors
  • Viral Nonstructural Proteins / chemistry*
  • Viral Nonstructural Proteins / metabolism

Substances

  • Cysteine Proteinase Inhibitors
  • Ligands
  • Viral Nonstructural Proteins
  • 3C-like proteinase, Coronavirus
  • Cysteine Endopeptidases

Supplementary concepts

  • severe acute respiratory syndrome coronavirus 2