Access
To read this story in full you will need to login or make a payment (see right).
Letter
Nature 442, 831-835 (17 August 2006) | doi:10.1038/nature04975; Received 8 May 2006; Accepted 9 June 2006; Published online 23 July 2006
Open Innovation Challenges
-
Efficient Chromosome Doubling: Plant Cell Division
The Seeker is looking for an efficient chromosome doubling method in plants and in particular, metho...
-
Protect Enzyme from In Planta Degradation
A proposal for stable expression of an enzyme in corn seed is desired.
nature jobs
Associate Professor / Professor ? NCRIS TERN Director
- University Of Queensland, Australia
- Brisbane, Queensland, Australia
Molecular Biology Team Leader
- AstraZeneca
- Alderley, Cheshire United Kingdom
Structure of the catalytic domain of the hepatitis C virus NS2-3 protease
Ivo C. Lorenz1,2, Joseph Marcotrigiano1,2, Thomas G. Dentzer1 & Charles M. Rice1
- Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA
- *These authors contributed equally to this work
Correspondence to: Joseph Marcotrigiano1,2Charles M. Rice1 Correspondence and requests for materials should be addressed to C.M.R. (Email: ricec@rockefeller.edu) or J.M. (Email: marcotj@rockefeller.edu).
Abstract
Hepatitis C virus is a major global health problem affecting an estimated 170 million people worldwide1. Chronic infection is common and can lead to cirrhosis and liver cancer. There is no vaccine available and current therapies have met with limited success2. The viral RNA genome encodes a polyprotein that includes two proteases essential for virus replication3, 4. 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 fold5, 6, but the enzymatic mechanism of the NS2-3 protease remains unresolved7, 8, 9. Here we report the crystal structure of the catalytic domain of the NS2-3 protease at 2.3 Å 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.
To read this story in full you will need to login or make a payment (see right).
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
RESEARCH
X-ray structure of 5-aminolaevulinate dehydratase, a hybrid aldolaseNature Structural Biology Article (01 Dec 1997)
A GTP-binding adapter protein couples TRAIL receptors to apoptosis-inducing proteinsNature Immunology Article (01 Jun 2001)
Structure of Sindbis virus core protein reveals a chymotrypsin-like serine proteinase and the organization of the virionNature Article (07 Nov 1991)
Structure of the zinc-binding domain of an essential component of the hepatitis C virus replicaseNature Letters to Editor (19 May 2005)
See all 18 matches for Research
