7ALI
Crystal structure of the main protease (3CLpro/Mpro) of SARS-CoV-2 at 1.65A resolution (spacegroup P2(1)).
Summary for 7ALI
| Entry DOI | 10.2210/pdb7ali/pdb |
| Related | 7ALH |
| Descriptor | 3C-like proteinase (2 entities in total) |
| Functional Keywords | sars-cov-2, mpro, 3clpro, exscalate4cov, drug discovery, elettra, viral protein |
| Biological source | Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2) |
| Total number of polymer chains | 2 |
| Total formula weight | 67651.09 |
| Authors | Costanzi, E.,Demitri, N.,Giabbai, B.,Heroux, A.,Storici, P. (deposition date: 2020-10-06, release date: 2020-12-02, Last modification date: 2024-01-31) |
| Primary citation | Costanzi, E.,Kuzikov, M.,Esposito, F.,Albani, S.,Demitri, N.,Giabbai, B.,Camasta, M.,Tramontano, E.,Rossetti, G.,Zaliani, A.,Storici, P. Structural and Biochemical Analysis of the Dual Inhibition of MG-132 against SARS-CoV-2 Main Protease (Mpro/3CLpro) and Human Cathepsin-L. Int J Mol Sci, 22:-, 2021 Cited by PubMed Abstract: After almost two years from its first evidence, the COVID-19 pandemic continues to afflict people worldwide, highlighting the need for multiple antiviral strategies. SARS-CoV-2 main protease (Mpro/3CLpro) is a recognized promising target for the development of effective drugs. Because single target inhibition might not be sufficient to block SARS-CoV-2 infection and replication, multi enzymatic-based therapies may provide a better strategy. Here we present a structural and biochemical characterization of the binding mode of MG-132 to both the main protease of SARS-CoV-2, and to the human Cathepsin-L, suggesting thus an interesting scaffold for the development of double-inhibitors. X-ray diffraction data show that MG-132 well fits into the Mpro active site, forming a covalent bond with Cys145 independently from reducing agents and crystallization conditions. Docking of MG-132 into Cathepsin-L well-matches with a covalent binding to the catalytic cysteine. Accordingly, MG-132 inhibits Cathepsin-L with nanomolar potency and reversibly inhibits Mpro with micromolar potency, but with a prolonged residency time. We compared the apo and MG-132-inhibited structures of Mpro solved in different space groups and we identified a new apo structure that features several similarities with the inhibited ones, offering interesting perspectives for future drug design and in silico efforts. PubMed: 34769210DOI: 10.3390/ijms222111779 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.65 Å) |
Structure validation
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