NS3-4A OF HEPATITIS-C VIRUS IS A CHYMOTRYPSIN-LIKE PROTEASE
SCIE
SCOPUS
- Title
- NS3-4A OF HEPATITIS-C VIRUS IS A CHYMOTRYPSIN-LIKE PROTEASE
- Authors
- HAHM, B; HAN, DS; BACK, SH; SONG, OK; CHO, MJ; KIM, CJ; SHIMOTOHNO, K; JANG, SK
- Date Issued
- 1995-04
- Publisher
- AMER SOC MICROBIOLOGY
- Abstract
- The polyprotein encoded by a single open reading frame of hepatitis C virus (HCV) is processed by host- and virus-encoded proteases. The viral protease NS3 is responsible for the cleavage of at least four sites (NS3/4A, NS4A/4B, NS4B/5A, and NS5A/5B junctions) in the nonstructural protein region. To characterize the protease function of NS3 and NS4 on various target sites, efficient cis- and trans-cleavage assay systems were developed by using in vitro transcription and translation. Deletion of the C-terminal two-thirds from NS3 in an NS3-NS4A-4B polypeptide (NS3 Delta C-4A-4B) hampered cleavage of the NS3/4A junction but not that of the NS4A/4B junction. As a consequence, expression of NS3 Delta C-4A-4B containing an internal deletion of NS3 results in an NS3 Delta C-4A fusion protein. NS3 Delta C-4A shows very efficient and specific trans-cleavage activity at NS4A/4B, NS4B/5A, and NS5A/5B junctions. In addition, the biochemical properties of HCV NS3 Delta C-4A were further elucidated by adding known protease inhibitors in trans-cleavage reactions. The HCV protease NS3-4A is inhibited by chymotrypsin-specific inhibitors N-tosyl-L-phenylalanine chloromethyl ketone (TPCK), chymostatin, and Pefabloc SC but not by trypsin-like protease inhibitors antipain, leupeptin, and N-alpha-p-tosyl-L-lysine chloromethyl ketone (TLCK) or by the protease inhibitors E-64, bestatin, pepstatin, and phosphoramidon. This finding strongly suggests that HCV protease NS3-4A is a chymotrypsin-like serine protease.
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/11300
- DOI
- 10.1128/JVI.69.4.2534-2539.1995
- ISSN
- 0022-538X
- Article Type
- Article
- Citation
- JOURNAL OF VIROLOGY, vol. 69, no. 4, page. 2534 - 2539, 1995-04
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