1. Structure of the Main Protease from a Global Infectious Human Coronavirus, HCoV-HKU1
- Author
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Fei Xue, Mark Bartlam, Qi Zhao, Shuang Li, Zihe Rao, Cheng Chen, and Yilong Zou
- Subjects
Models, Molecular ,Polyproteins ,DNA, Complementary ,Protein Conformation ,medicine.medical_treatment ,viruses ,Immunology ,Molecular Sequence Data ,RNA-dependent RNA polymerase ,medicine.disease_cause ,Microbiology ,Protein Structure, Secondary ,Substrate Specificity ,stomatognathic system ,X-Ray Diffraction ,Nidovirales ,Leucine ,Virology ,medicine ,Escherichia coli ,Coronaviridae ,Humans ,Amino Acid Sequence ,Coronavirus ,Protease ,Binding Sites ,biology ,Sequence Homology, Amino Acid ,Structure and Assembly ,virus diseases ,Hydrogen Bonding ,biology.organism_classification ,respiratory tract diseases ,Oxygen ,Kinetics ,Viral replication ,Insect Science ,Human coronavirus HKU1 ,Coronavirus Infections ,Peptide Hydrolases ,Plasmids ,Protein Binding - Abstract
The newly emergent human coronavirus HKU1 (HCoV-HKU1) was first identified in Hong Kong in 2005. Infection by HCoV-HKU1 occurs worldwide and causes syndromes such as the common cold, bronchitis, and pneumonia. The CoV main protease (M pro ), which is a key enzyme in viral replication via the proteolytic processing of the replicase polyproteins, has been recognized as an attractive target for rational drug design. In this study, we report the structure of HCoV-HKU1 M pro in complex with a Michael acceptor, inhibitor N3. The structure of HCoV-HKU1 provides a high-quality model for group 2A CoVs, which are distinct from group 2B CoVs such as severe acute respiratory syndrome CoV. The structure, together with activity assays, supports the relative conservation at the P1 position that was discovered by sequencing the HCoV-HKU1 genome. Combined with structural data from other CoV M pro s, the HCoV-HKU1 M pro structure reported here provides insights into both substrate preference and the design of antivirals targeting CoVs.
- Published
- 2008
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