8QDC

Crystal structure of SARS-CoV-2 main protease (MPro) in complex with the covalent inhibitor GUE-3642 (compound 1 in publication)

Summary for 8QDC

• Entry DOI: 10.2210/pdb8qdc/pdb
• Descriptor: 3C-like proteinase nsp5, (phenylmethyl) ~{N}-[(2~{S})-1-[[(2~{S})-1-[[(2~{S})-1-[[iminomethyl-(phenylmethyl)amino]-methyl-amino]-1-oxidanylidene-3-phenyl-propan-2-yl]amino]-3,3-dimethyl-1-oxidanylidene-butan-2-yl]amino]-1-oxidanylidene-butan-2-yl]carbamate, DIMETHYL SULFOXIDE, ... (5 entities in total)
• Functional Keywords: sars-ncov, main protease, covalent inhibitor, viral protein
• Biological source: Severe acute respiratory syndrome coronavirus
• Total number of polymer chains: 2
• Total formula weight: 69050.26

Authors

Strater, N.,Claff, T.,Sylvester, K.,Mueller, C.E.,Guetschow, M. (deposition date: 2023-08-28, release date: 2024-07-03, Last modification date: 2024-11-13)

Primary citation

Voget, R.,Breidenbach, J.,Claff, T.,Hingst, A.,Sylvester, K.,Steinebach, C.,Vu, L.P.,Weisse, R.H.,Bartz, U.,Strater, N.,Muller, C.E.,Gutschow, M.
Development of an active-site titrant for SARS-CoV-2 main protease as an indispensable tool for evaluating enzyme kinetics.
Acta Pharm Sin B, 14:2349-2357, 2024

PubMed Abstract: A titrant for the SARS-CoV-2 main protease (M) was developed that enables, for the first time, the exact determination of the concentration of the enzymatically active M by active-site titration. The covalent binding mode of the tetrapeptidic titrant was elucidated by the determination of the crystal structure of the enzyme-titrant complex. Four fluorogenic substrates of M, including a prototypical, internally quenched Dabcyl-EDANS peptide, were compared in terms of solubility under typical assay conditions. By exploiting the new titrant, key kinetic parameters for the M-catalyzed cleavage of these substrates were determined.

PubMed: 38799620
DOI: 10.1016/j.apsb.2024.03.001

Experimental method

X-RAY DIFFRACTION (1.77 Å)