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| - | [[Image:2hd0.gif|left|200px]] | + | {{Seed}} |
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| | {{STRUCTURE_2hd0| PDB=2hd0 | SCENE= }} | | {{STRUCTURE_2hd0| PDB=2hd0 | SCENE= }} |
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| - | '''Structure of the catalytic domain of hepatitis C virus NS2'''
| + | ===Structure of the catalytic domain of hepatitis C virus NS2=== |
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| - | ==Overview==
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| - | 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.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_16862121}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 16862121 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_16862121}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Cysteine protease]] | | [[Category: Cysteine protease]] |
| | [[Category: Dimer]] | | [[Category: Dimer]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 06:08:15 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 00:35:34 2008'' |
Revision as of 21:35, 27 July 2008
Template:STRUCTURE 2hd0
Structure of the catalytic domain of hepatitis C virus NS2
Template:ABSTRACT PUBMED 16862121
About this Structure
2HD0 is a Single protein structure of sequence from Hepatitis c virus. 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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