8dd6 | pdb_00008dd6

SARS-CoV-2 Main Protease (Mpro) H163A Mutant in Complex with GC376

spinqualitylabelsall models 8dd6, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8dd6 is a 1 chain structure with sequence from Severe acute respiratory syndrome coronavirus 2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.3Å Ligands: DMS, K36 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A7U3EDN3_SARS2 Publication Abstract from PubMed The main protease of SARS-CoV-2 (Mpro) is an important target for developing COVID-19 therapeutics. Recent work has highlighted Mpro's susceptibility to undergo redox-associated conformational changes in response to cellular and immune-system-induced oxidation. Despite structural evidence indicating large-scale rearrangements upon oxidation, the mechanisms of conformational change and its functional consequences are poorly understood. Here, we present the crystal structure of an Mpro point mutant (H163A) that shows an oxidized conformation with the catalytic cysteine in a disulfide bond. We hypothesize that Mpro adopts this conformation under oxidative stress to protect against over-oxidation. Our metadynamics simulations illustrate a potential mechanism by which H163 modulates this transition and suggest that this equilibrium exists in the wild type enzyme. We show that other point mutations also significantly shift the equilibrium towards this state by altering conformational free energies. Unique avenues of SARS-CoV-2 research can be explored by understanding how H163 modulates this equilibrium. The H163A mutation unravels an oxidized conformation of the SARS-CoV-2 main protease.,Tran N, Dasari S, Barwell SAE, McLeod MJ, Kalyaanamoorthy S, Holyoak T, Ganesan A Nat Commun. 2023 Sep 12;14(1):5625. doi: 10.1038/s41467-023-40023-4. PMID:37699927 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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