9EZ6
Complex of a mutant of the SARS-CoV-2 main protease Mpro with the nsp14/15 substrate peptide.
Summary for 9EZ6
| Entry DOI | 10.2210/pdb9ez6/pdb |
| Related | 9EX8 9EXU 9EYA 9EZ4 |
| Descriptor | Replicase polyprotein 1a, THR-PHE-THR-ARG-LEU-GLN-SER-LEU-GLU-ASN, DIMETHYL SULFOXIDE, ... (8 entities in total) |
| Functional Keywords | sars-cov-2, main protease, nsp5, cys-peptidase, 3clpro, hydrolase |
| Biological source | Severe acute respiratory syndrome coronavirus 2 More |
| Total number of polymer chains | 3 |
| Total formula weight | 70172.76 |
| Authors | |
| Primary citation | Fornasier, E.,Fabbian, S.,Shehi, H.,Enderle, J.,Gatto, B.,Volpin, D.,Biondi, B.,Bellanda, M.,Giachin, G.,Sosic, A.,Battistutta, R. Allostery in homodimeric SARS-CoV-2 main protease. Commun Biol, 7:1435-1435, 2024 Cited by PubMed Abstract: Many enzymes work as homodimers with two distant catalytic sites, but the reason for this choice is often not clear. For the main protease M of SARS-CoV-2, dimerization is essential for function and plays a regulatory role during the coronaviral replication process. Here, to analyze a possible allosteric mechanism, we use X-ray crystallography, native mass spectrometry, isothermal titration calorimetry, and activity assays to study the interaction of M with three peptide substrates. Crystal structures show how the plasticity of M is exploited to face differences in the sequences of the natural substrates. Importantly, unlike in the free form, the M dimer in complex with these peptides is asymmetric and the structures of the substrates nsp5/6 and nsp14/15 bound to a single subunit show allosteric communications between active sites. We identified arginines 4 and 298 as key elements in the transition from symmetric to asymmetric dimers. Kinetic data allowed the identification of positive cooperativity based on the increase in the processing efficiency (kinetic allostery) and not on the better binding of the substrates (thermodynamic allostery). At the physiological level, this allosteric behavior may be justified by the need to regulate the processing of viral polyproteins in time and space. PubMed: 39496839DOI: 10.1038/s42003-024-07138-w PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.87 Å) |
Structure validation
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