2hd0
From Proteopedia
(New page: 200px<br /><applet load="2hd0" size="450" color="white" frame="true" align="right" spinBox="true" caption="2hd0, resolution 2.28Å" /> '''Structure of the cat...) |
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| - | [[Image:2hd0.gif|left|200px]]<br /><applet load="2hd0" size=" | + | [[Image:2hd0.gif|left|200px]]<br /><applet load="2hd0" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2hd0, resolution 2.28Å" /> | caption="2hd0, resolution 2.28Å" /> | ||
'''Structure of the catalytic domain of hepatitis C virus NS2'''<br /> | '''Structure of the catalytic domain of hepatitis C virus NS2'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Hepatitis C virus is a major global health problem affecting an estimated | + | Hepatitis C virus is a major global health problem affecting an estimated 170 million people worldwide. Chronic infection is common and can lead to cirrhosis and liver cancer. There is no vaccine available and current therapies have met with limited success. The viral RNA genome encodes a polyprotein that includes two proteases essential for virus replication. The NS2-3 protease mediates a single cleavage at the NS2/NS3 junction, whereas the NS3-4A protease cleaves at four downstream sites in the polyprotein. NS3-4A is characterized as a serine protease with a chymotrypsin-like fold, but the enzymatic mechanism of the NS2-3 protease remains unresolved. Here we report the crystal structure of the catalytic domain of the NS2-3 protease at 2.3 A resolution. The structure reveals a dimeric cysteine protease with two composite active sites. For each active site, the catalytic histidine and glutamate residues are contributed by one monomer, and the nucleophilic cysteine by the other. The carboxy-terminal residues remain coordinated in the two active sites, predicting an inactive post-cleavage form. Proteolysis through formation of a composite active site occurs in the context of the viral polyprotein expressed in mammalian cells. These features offer unexpected insights into polyprotein processing by hepatitis C virus and new opportunities for antiviral drug design. |
==About this Structure== | ==About this Structure== | ||
| - | 2HD0 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Hepatitis_c_virus Hepatitis c virus] with DMU and BOG as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 2HD0 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Hepatitis_c_virus Hepatitis c virus] with <scene name='pdbligand=DMU:'>DMU</scene> and <scene name='pdbligand=BOG:'>BOG</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HD0 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Hepatitis c virus]] | [[Category: Hepatitis c virus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Lorenz, I | + | [[Category: Lorenz, I C.]] |
[[Category: Marcotrigiano, J.]] | [[Category: Marcotrigiano, J.]] | ||
| - | [[Category: Rice, C | + | [[Category: Rice, C M.]] |
[[Category: BOG]] | [[Category: BOG]] | ||
[[Category: DMU]] | [[Category: DMU]] | ||
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[[Category: dimer]] | [[Category: dimer]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:40:35 2008'' |
Revision as of 15:40, 21 February 2008
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Structure of the catalytic domain of hepatitis C virus NS2
Overview
Hepatitis C virus is a major global health problem affecting an estimated 170 million people worldwide. Chronic infection is common and can lead to cirrhosis and liver cancer. There is no vaccine available and current therapies have met with limited success. The viral RNA genome encodes a polyprotein that includes two proteases essential for virus replication. The NS2-3 protease mediates a single cleavage at the NS2/NS3 junction, whereas the NS3-4A protease cleaves at four downstream sites in the polyprotein. NS3-4A is characterized as a serine protease with a chymotrypsin-like fold, but the enzymatic mechanism of the NS2-3 protease remains unresolved. Here we report the crystal structure of the catalytic domain of the NS2-3 protease at 2.3 A resolution. The structure reveals a dimeric cysteine protease with two composite active sites. For each active site, the catalytic histidine and glutamate residues are contributed by one monomer, and the nucleophilic cysteine by the other. The carboxy-terminal residues remain coordinated in the two active sites, predicting an inactive post-cleavage form. Proteolysis through formation of a composite active site occurs in the context of the viral polyprotein expressed in mammalian cells. These features offer unexpected insights into polyprotein processing by hepatitis C virus and new opportunities for antiviral drug design.
About this Structure
2HD0 is a Single protein structure of sequence from Hepatitis c virus with and as ligands. Full crystallographic information is available from OCA.
Reference
Structure of the catalytic domain of the hepatitis C virus NS2-3 protease., Lorenz IC, Marcotrigiano J, Dentzer TG, Rice CM, Nature. 2006 Aug 17;442(7104):831-5. Epub 2006 Jul 23. PMID:16862121
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