7Z59
SARS-CoV-2 main protease (Mpro) covalently modified with a penicillin derivative
Summary for 7Z59
| Entry DOI | 10.2210/pdb7z59/pdb |
| Descriptor | 3C-like proteinase nsp5, (3S)-4-[[2,4-bis(fluoranyl)phenyl]methoxy]-2-methyl-4-oxidanylidene-3-[[(Z)-3-oxidanylidene-2-(2-phenoxyethanoylamino)prop-1-enyl]amino]butane-2-sulfinic acid, 1,2-ETHANEDIOL, ... (4 entities in total) |
| Functional Keywords | inhibitor complex, viral protein |
| Biological source | Severe acute respiratory syndrome coronavirus 2 |
| Total number of polymer chains | 1 |
| Total formula weight | 34269.99 |
| Authors | Owen, C.D.,Malla, T.R.,Brewitz, L.,Lukacik, P.,Strain-Damerell, C.,Mikolajek, H.,Muntean, D.G.,Aslam, H.,Salah, E.,Tumber, A.,Schofield, C.J.,Walsh, M.A. (deposition date: 2022-03-08, release date: 2022-06-29, Last modification date: 2024-10-23) |
| Primary citation | Malla, T.R.,Brewitz, L.,Muntean, D.G.,Aslam, H.,Owen, C.D.,Salah, E.,Tumber, A.,Lukacik, P.,Strain-Damerell, C.,Mikolajek, H.,Walsh, M.A.,Schofield, C.J. Penicillin Derivatives Inhibit the SARS-CoV-2 Main Protease by Reaction with Its Nucleophilic Cysteine. J.Med.Chem., 65:7682-7696, 2022 Cited by PubMed Abstract: The SARS-CoV-2 main protease (M) is a medicinal chemistry target for COVID-19 treatment. Given the clinical efficacy of β-lactams as inhibitors of bacterial nucleophilic enzymes, they are of interest as inhibitors of viral nucleophilic serine and cysteine proteases. We describe the synthesis of penicillin derivatives which are potent M inhibitors and investigate their mechanism of inhibition using mass spectrometric and crystallographic analyses. The results suggest that β-lactams have considerable potential as M inhibitors via a mechanism involving reaction with the nucleophilic cysteine to form a stable acyl-enzyme complex as shown by crystallographic analysis. The results highlight the potential for inhibition of viral proteases employing nucleophilic catalysis by β-lactams and related acylating agents. PubMed: 35549342DOI: 10.1021/acs.jmedchem.1c02214 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
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