2amq
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(New page: 200px<br /><applet load="2amq" size="450" color="white" frame="true" align="right" spinBox="true" caption="2amq, resolution 2.3Å" /> '''Crystal Structure Of ...)
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Revision as of 06:06, 21 November 2007
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Crystal Structure Of SARS_CoV Mpro in Complex with an Inhibitor N3
Overview
The genus Coronavirus contains about 25 species of coronaviruses (CoVs), which are important pathogens causing highly prevalent diseases and often, severe or fatal in humans and animals. No licensed specific drugs are, available to prevent their infection. Different host receptors for, cellular entry, poorly conserved structural proteins (antigens), and the, high mutation and recombination rates of CoVs pose a significant problem, in the development of wide-spectrum anti-CoV drugs and vaccines. CoV main, proteases (M(pro)s), which are key enzymes in viral gene expression and, replication, were revealed to share a highly conservative, substrate-recognition pocket by comparison of four crystal structures and, a homology model representing all three genetic clusters of the genus, Coronavirus. This conclusion was further supported by enzyme activity, assays. Mechanism-based irreversible inhibitors were designed, based on, this conserved structural region, and a uniform inhibition mechanism was, elucidated from the structures of Mpro-inhibitor complexes from severe, acute respiratory syndrome-CoV and porcine transmissible gastroenteritis, virus. A structure-assisted optimization program has yielded compounds, with fast in vitro inactivation of multiple CoV M(pro)s, potent antiviral, activity, and extremely low cellular toxicity in cell-based assays., Further modification could rapidly lead to the discovery of a single agent, with clinical potential against existing and possible future emerging, CoV-related diseases.
About this Structure
2AMQ is a Single protein structure of sequence from Human sars coronavirus with 3IH as ligand. Full crystallographic information is available from OCA.
Reference
Design of wide-spectrum inhibitors targeting coronavirus main proteases., Yang H, Xie W, Xue X, Yang K, Ma J, Liang W, Zhao Q, Zhou Z, Pei D, Ziebuhr J, Hilgenfeld R, Yuen KY, Wong L, Gao G, Chen S, Chen Z, Ma D, Bartlam M, Rao Z, PLoS Biol. 2005 Oct;3(10):e324. Epub 2005 Sep 6. PMID:16128623
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