2V6N

Crystal structures of the SARS-coronavirus main proteinase inactivated by benzotriazole compounds

2V6N の概要

• エントリーDOI: 10.2210/pdb2v6n/pdb
• 分子名称: REPLICASE POLYPROTEIN 1AB, 4-(DIMETHYLAMINO)BENZOIC ACID, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, ... (5 entities in total)
• 機能のキーワード: thiol protease, rna replication, main proteinase, ribosomal frameshift, sars, protease, hydrolase, polyprotein, viral protein
• 由来する生物種: HUMAN SARS CORONAVIRUS (SARS-COV)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 34333.13

構造登録者

Verschueren, K.H.G.,Pumpor, K.,Anemueller, S.,Mesters, J.R.,Hilgenfeld, R. (登録日: 2007-07-19, 公開日: 2008-07-01, 最終更新日: 2024-10-16)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.98 Å)