2VJ1

A Structural View of the Inactivation of the SARS-Coronavirus Main Proteinase by Benzotriazole Esters

Replaces:  2CGG

Summary for 2VJ1

• Entry DOI: 10.2210/pdb2vj1/pdb
• Descriptor: SARS CORONAVIRUS MAIN PROTEINASE, DIMETHYL SULFOXIDE, BENZOIC ACID, ... (5 entities in total)
• Functional Keywords: sars, protease, hydrolase, polyprotein, thiol protease, ribosomal frameshift, sars coronavirus main proteinase
• Biological source: HUMAN SARS CORONAVIRUS
• Total number of polymer chains: 2
• Total formula weight: 69207.97

Authors

Verschueren, K.H.G.,Pumpor, K.,Anemueller, S.,Mesters, J.R.,Hilgenfeld, R. (deposition date: 2007-12-06, release date: 2008-07-01, Last modification date: 2023-12-13)

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

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: 18559270
DOI: 10.1016/J.CHEMBIOL.2008.04.011

Experimental method

X-RAY DIFFRACTION (2.25 Å)