The crystal structures of severe acute respiratory syndrome virus main protease and its complex with an inhibitor

• DOI: 10.1073/pnas.1835675100
• Publication Date: 2003-11-16T20:42:47Z
• Authors: Haitao Yang; Maojun Yang; Yi Ding; Yiwei Liu; Zhiyong Lou; Zhe Zhou; Lei Sun; Lijuan Mo; Sheng Ye; Hai Pang; George F. Gao; Kanchan Anand; Mark Bartlam; Rolf Hilgenfeld; Zihe Rao
• Keywords: Polyproteins; Coronavirus; Protease inhibitor (pharmacology)

A newly identified severe acute respiratory syndrome coronavirus (SARS-CoV), is the etiological agent responsible for outbreak of SARS. The SARS-CoV main protease, which a 33.8-kDa protease (also called 3C-like protease), plays pivotal role in mediating viral replication and transcription functions through extensive proteolytic processing two replicase polyproteins, pp1a (486 kDa) pp1ab (790 kDa). Here, we report crystal structures at different pH values complex with specific inhibitor. structure has fold that can be described as an augmented serine-protease, but Cys-His active site. This series structures, first, to our knowledge, any protein from SARS virus, reveal substantial pH-dependent conformational changes, unexpected mode inhibitor binding, providing structural basis rational drug design.