1UK4

Crystal structure of SARS Coronavirus Main Proteinase (3CLpro) Complexed With An Inhibitor

Summary for 1UK4

• Entry DOI: 10.2210/pdb1uk4/pdb
• Related: 1UK2 1UK3
• Descriptor: 3C-like proteinase nsp5, 5-mer peptide of inhibitor (3 entities in total)
• Functional Keywords: anti-parallel b-barrel, anti-parallel a-helices, an inhibitor, hydrolase
• Biological source: SARS coronavirus; More
• Cellular location: Non-structural protein 3: Host membrane; Multi-pass membrane protein (Potential). Non-structural protein 4: Host membrane; Multi-pass membrane protein (Potential). Non-structural protein 6: Host membrane; Multi-pass membrane protein (Potential). Non-structural protein 7: Host cytoplasm, host perinuclear region (By similarity). Non-structural protein 8: Host cytoplasm, host perinuclear region (By similarity). Non-structural protein 9: Host cytoplasm, host perinuclear region (By similarity). Non-structural protein 10: Host cytoplasm, host perinuclear region (By similarity). Helicase: Host endoplasmic reticulum-Golgi intermediate compartment (Potential). Uridylate-specific endoribonuclease: Host cytoplasm, host perinuclear region (By similarity): P0C6X7
• Total number of polymer chains: 5
• Total formula weight: 69535.45

Authors

Yang, H.,Yang, M.,Liu, Y.,Bartlam, M.,Ding, Y.,Lou, Z.,Sun, L.,Zhou, Z.,Ye, S.,Anand, K.,Pang, H.,Gao, G.F.,Hilgenfeld, R.,Rao, Z. (deposition date: 2003-08-14, release date: 2003-11-18, Last modification date: 2024-11-13)

Primary citation

Yang, H.,Yang, M.,Ding, Y.,Liu, Y.,Lou, Z.,Zhou, Z.,Sun, L.,Mo, L.,Ye, S.,Pang, H.,Gao, G.F.,Anand, K.,Bartlam, M.,Hilgenfeld, R.,Rao, Z.
The crystal structures of severe acute respiratory syndrome virus main protease and its complex with an inhibitor
Proc.Natl.Acad.Sci.USA, 100:13190-13195, 2003

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

PubMed: 14585926
DOI: 10.1073/pnas.1835675100

Experimental method

X-RAY DIFFRACTION (2.5 Å)