7JME
Structure of the SARS-CoV-2 NSP3 Macro X domain in complex with cyclic AMP
Summary for 7JME
| Entry DOI | 10.2210/pdb7jme/pdb |
| Descriptor | Non-structural protein 3, ADENOSINE-3',5'-CYCLIC-MONOPHOSPHATE (3 entities in total) |
| Functional Keywords | macro domain, camp, cyclic amp, viral protein, sars-cov-2, viral protein-inhibitor complex, viral protein/inhibitor |
| Biological source | Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2, COVID-19 virus) |
| Total number of polymer chains | 1 |
| Total formula weight | 18823.31 |
| Authors | Vuksanovic, N.,Melkonian, T.R.,Silvaggi, N.R. (deposition date: 2020-07-31, release date: 2020-09-02, Last modification date: 2023-10-18) |
| Primary citation | Virdi, R.S.,Bavisotto, R.V.,Hopper, N.C.,Vuksanovic, N.,Melkonian, T.R.,Silvaggi, N.R.,Frick, D.N. Discovery of Drug-Like Ligands for the Mac1 Domain of SARS-CoV-2 Nsp3. Slas Discov, 25:1162-1170, 2020 Cited by PubMed Abstract: Small molecules that bind the SARS-CoV-2 nonstructural protein 3 Mac1 domain in place of ADP-ribose could be useful as molecular probes or scaffolds for COVID-19 antiviral drug discovery because Mac1 has been linked to the ability of coronaviruses to evade cellular detection. A high-throughput assay based on differential scanning fluorimetry (DSF) was therefore optimized and used to identify possible Mac1 ligands in small libraries of drugs and drug-like compounds. Numerous promising compounds included nucleotides, steroids, β-lactams, and benzimidazoles. The main drawback to this approach was that a high percentage of compounds in some libraries were found to influence the observed Mac1 melting temperature. To prioritize DSF screening hits, the shapes of the observed melting curves and initial assay fluorescence were examined, and the results were compared with virtual screens performed using AutoDock Vina. The molecular basis for alternate ligand binding was also examined by determining a structure of one of the hits, cyclic adenosine monophosphate, with atomic resolution. PubMed: 32981460DOI: 10.1177/2472555220960428 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.55 Å) |
Structure validation
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