2d2d
From Proteopedia
(New page: 200px<br /><applet load="2d2d" size="450" color="white" frame="true" align="right" spinBox="true" caption="2d2d, resolution 2.7Å" /> '''Crystal Structure Of ...) |
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| - | [[Image:2d2d.gif|left|200px]]<br /><applet load="2d2d" size=" | + | [[Image:2d2d.gif|left|200px]]<br /><applet load="2d2d" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2d2d, resolution 2.7Å" /> | caption="2d2d, resolution 2.7Å" /> | ||
'''Crystal Structure Of SARS-CoV Mpro in Complex with an Inhibitor I2'''<br /> | '''Crystal Structure Of SARS-CoV Mpro in Complex with an Inhibitor I2'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The genus Coronavirus contains about 25 species of coronaviruses (CoVs), which are important pathogens causing highly prevalent diseases and often | + | 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== | ==About this Structure== | ||
| - | 2D2D is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Human_sars_coronavirus Human sars coronavirus] with ENB as [http://en.wikipedia.org/wiki/ligand ligand]. This structure | + | 2D2D is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Human_sars_coronavirus Human sars coronavirus] with <scene name='pdbligand=ENB:'>ENB</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. This structure supersedes the now removed PDB entry 1WNQ. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2D2D OCA]. |
==Reference== | ==Reference== | ||
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[[Category: anti-parallel b-barrel]] | [[Category: anti-parallel b-barrel]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:54:40 2008'' |
Revision as of 14:54, 21 February 2008
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Crystal Structure Of SARS-CoV Mpro in Complex with an Inhibitor I2
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
2D2D is a Single protein structure of sequence from Human sars coronavirus with as ligand. This structure supersedes the now removed PDB entry 1WNQ. 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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