2V6N
Crystal structures of the SARS-coronavirus main proteinase inactivated by benzotriazole compounds
Summary for 2V6N
Entry DOI | 10.2210/pdb2v6n/pdb |
Descriptor | REPLICASE POLYPROTEIN 1AB, 4-(DIMETHYLAMINO)BENZOIC ACID, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, ... (5 entities in total) |
Functional Keywords | thiol protease, rna replication, main proteinase, ribosomal frameshift, sars, protease, hydrolase, polyprotein, viral protein |
Biological source | HUMAN SARS CORONAVIRUS (SARS-COV) |
Total number of polymer chains | 1 |
Total formula weight | 34333.13 |
Authors | Verschueren, K.H.G.,Pumpor, K.,Anemueller, S.,Mesters, J.R.,Hilgenfeld, R. (deposition date: 2007-07-19, release date: 2008-07-01, Last modification date: 2024-10-16) |
Primary citation | Verschueren, K.H.G.,Pumpor, K.,Anemueller, S.,Chen, S.,Mesters, J.R.,Hilgenfeld, R. A Structural View of the Inactivation of the Sars Coronavirus Main Proteinase by Benzotriazole Esters. Chem.Biol., 15:597-, 2008 Cited by PubMed Abstract: The main proteinase (M(pro)) of the severe acute respiratory syndrome (SARS) coronavirus is a principal target for the design of anticoronaviral compounds. Benzotriazole esters have been reported as potent nonpeptidic inhibitors of the enzyme, but their exact mechanism of action remains unclear. Here we present crystal structures of SARS-CoV M(pro), the active-site cysteine of which has been acylated by benzotriazole esters that act as suicide inhibitors. In one of the structures, the thioester product has been hydrolyzed and benzoic acid is observed to bind to the hydrophobic S2 pocket. This structure also features the enzyme with a shortened N-terminal segment ("amputated N finger"). The results further the understanding of the important role of the N finger for catalysis as well as the design of benzotriazole inhibitors with improved specificity. PubMed: 18559270DOI: 10.1016/J.CHEMBIOL.2008.04.011 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (1.98 Å) |
Structure validation
Download full validation report