Family C5


Summary Holotypes Alignment Tree Genomes Structure Literature

Summary for family C5

NamePeptidase family C5 (adenain family)
Family type peptidaseC05.001 - adenain (human adenovirus type 2), MEROPS Accession MER0000802 (peptidase unit: 1-204)
Content of familyPeptidase family C5 contains the endopeptidase adenain.
History Identifier created: Biochem.J. 290:205-218 (1993)
An early indication of the existence of the adenovirus processing enzyme was reported by Anderson et al. (1973), and further progress was made on the characterisation of the enzyme by Weber and co-workers (e.g. Weber, 1976; Bhatti & Weber, 1979). The gene encoding adenain was sequenced by Kruijer et al. (1980).
Catalytic typeCysteine
Active site residuesH54 D,E71 Q115 C122 
Active siteThe catalytic residues of family C5 have been identified as His and Cys, forming the catalytic dyad. Two other active site residues are found, a Gln residue preceding the catalytic Cys and a Glu residue preceding the catalytic His (see the Alignment). These have similar roles to the Gln19 and Asn175 residues in papain (C01.001) which are responsible for the formation of the oxyanion hole and in the orientation of the imidazolium ring of the catalytic His respectively.
Activities and specificitiesAdenain is highly selective, cleaving Xaa-Xbb-Gly-Xbb-Xbb type bonds, where Xaa is Met, Leu or Ile and Xbb is any amino acid (Webster et al., 1989; Anderson, 1990; Weber, 1995). A eleven-residue virally encoded cofactor (GVQSLKRRRCF in human adenovirus 2) is required for activity (Webster et al., 1994), and activity is further enhanced by the interaction of the peptidase with DNA.
InhibitorsAdenain resembles papain in its inhibition by peptide nitrilies, but is resistant to E64 (Sircar et al., 1998). 2,4,5,7-Tetranitro-9-fluorenone has been described as an inhibitor of adenain (Pang et al., 2001).
Molecular structureThe tertiary structure of adenain shows an alpha/beta fold with the cofactor becoming the sixth strand of the beta sheet. The geometry of the catalytic site of adenain is similar to that of papain. However, the catalytic residues are in the order His, Cys and the fold of the protein is distinct (Ding et al., 1996). SCOP classify adenain and papain in the same superfamily on the basis that adenain has undergone a circular permutation of the catalytic core.
Basis of clan assignmentType family of clan CE.
Distribution of family Bacteria -  
Archaea -  
Protozoa -  
Fungi -  
Plants -  
Animals details  
Viruses details  
Biological functionsAdenain processes the virus protein precursors by removing an N-terminal propeptide (Weber & Tihanyi, 1994). It also has protein-deubiquitinating activity (Balakirev et al., 2002).
Pharmaceutical and biotech relevanceAdenoviruses most commonly cause respiratory illness, but can also cause gastroenteritis, conjunctivitis and cystitis. Adenain is a potential drug target.
ReviewsWeber (2004)
Statistics for family C5Sequences:92
Identifiers with PDB entries:1
Downloadable files Sequence library (FastA format)
Sequence alignment (FastA format)
Phylogenetic tree (Newick format)
Peptidases and Homologues MEROPS ID Structure
family C5 non-peptidase homologuesnon-peptidase homologue-
family C5 unassigned peptidasesunassigned-