Family S29


Summary Holotypes Alignment Tree Genomes Structure Literature

Summary for family S29

NamePeptidase family S29 (hepacivirin family)
Family type peptidaseS29.001 - hepacivirin (hepatitis C virus), MEROPS Accession MER0000295 (peptidase unit: 1027-1282)
Content of familyPeptidase family S29 contains polyprotein-processing peptidases of hepatitis viruses.
History Identifier created: Methods Enzymol. 244:19-61 (1994)
The causative agent of hepatitis C was identified as recently as 1989 (Choo et al., 1989and has subsequently attracted a huge amount of research effort because of the clinical importance of the disease. The serine peptidase that the virus encodes is hepacivirin (S29.001).
Catalytic typeSerine
Active site residuesH1083 D1107 S1165 
Active siteThe His, Asp, Ser active site residues (see the Alignment) are typical of the serine peptidases in clan PA.
Activities and specificitiesProcessing at the NS3/NS4A boundary is an intramolecular event, and the subsequent cleavages are intermolecular. The P1 residue at each site is Cys or Thr (see Substrates for S29.001). The 54-residue NS4A protein also encoded by the virus is an activator of the enzyme, and various synthetic peptides have been shown to have similar activity (Steinkühler et al., 1996).
InhibitorsNumerous inhibitors have been designed for hepacivirin (see Literature for S29.001).
Molecular structureThe structure of the NS3 protein encoded by the hepatitis C virus (Yao et al., 1999) shows the serine peptidase in the N-terminal 180 residues and an RNA helicase formed by the C-terminal part of the protein. The two domains are connected by a single strand. The over all fold of hepacivirin is similar to that of chymotrypsin and other peptidases in family S1.
Basis of clan assignmentProtein fold of the peptidase unit for members of this family resembles that of chymotrypsin, the type example for clan PA.
Distribution of family Bacteria -  
Archaea -  
Protozoa -  
Fungi -  
Plants -  
Animals -  
Viruses details  
Biological functionsHepacivirin is responsible for the processing of all the sites downstream of the gene itself: NS3/NS4, NS4A/NS4B, NS4B/NS5A and NS5A/NS5B (Lohmann et al., 1996).
Pharmaceutical and biotech relevanceInhibitors of hepacivirin might well form the basis of effective drugs, since inactivation of the enzyme abolishes infectivity of the virus (Kolykhalov et al., 2000).
ReviewsSteinkuhler (2004)
Statistics for family S29Sequences:236
Identifiers with PDB entries:2
Downloadable files Sequence library (FastA format)
Sequence alignment (FastA format)
Phylogenetic tree (Newick format)
Other databases CATH
PFAM PF02907
SCOP 50596
Peptidases and Homologues MEROPS ID Structure
hepatitis G virus NS3 peptidaseS29.002-
non-peptidase homologue-
family S29 unassigned peptidasesunassignedYes