Family C28

Family

Summary Holotypes Alignment Tree Genomes Structure Literature

Summary for family C28

Family type peptidaseC28.001 - foot-and-mouth disease virus L-peptidase (foot-and-mouth disease virus), MEROPS Accession MER0002022 (peptidase unit: 1-201)
Content of familyPeptidase family C28 contains viral processing endopeptidases.
History Identifier created: Perspect.Drug Discov.Des. 6:1-11 (1996)
Two forms of the foot and mouth disease virus leader (L)-peptidase are known to exist. This is caused by two in-frame AUG codons at the beginning of the viral open reading frame. The two forms are named Lab and Lb, the Lb form being the shorter of the two proteins.
Catalytic typeCysteine
Active site residuesN47 C51 H148 D163 
Active siteThe active site residues are in the order Asn, Cys, His, Asp.
Activities and specificitiesThe Lb form of the L-peptidase cleaves the host initiation factor eIF-4G firstly at Gly479Arg480 and then at Lys318Arg319 (Kirchweger et al., 1995). The autocatalytic activity of L-peptidase at the L-VP4 scissile bond occurs at a LysGly bond.
InhibitorsBoth the cleavage of eIF-4G and the L-VP4 scissile bond are inhibited by E-64d in infected cells (Kleina & Grubman, 1992).
Molecular structureThe structure of the foot and mouth virus Lb peptidase was solved by Guarne et al., 1998. The catalytic domain is similar to other members of the papain clan, but contains a unique C-terminal extension Guarne et al., 2000. There are two domains with the active site residues found on opposite sides of the cleft separating the domains. Schlick et al., 2002 demonstrated that a different mechanism is used by the L-peptidase for stabilising and orientating the active site than is found in most papain-like peptidases, which involves an electrostatic charge on Asp164.
ClanCA
Basis of clan assignmentProtein fold of the peptidase unit for members of this family and resembles that of papain, the type example for clan CA.
Distribution of family Bacteria -  
Archaea -  
Protozoa -  
Fungi -  
Plants -  
Animals -  
Viruses details  
Biological functionsThe foot and mouth virus L-peptidase is involved in the processing of the viral polyprotein, autocatalytically releasing itself from its site at the N-terminus of the polyprotein. The function of the Lb peptidase is thought to be in the cleavage of the eukaryotic initiation factor elF-4G, which correlates with the switching off of most host cell protein synthesis (Grubman, 2004).
Statistics for family C28Sequences:29
Identifiers:2
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
foot-and-mouth disease virus L-peptidaseC28.001Yes
equine rhinovirus L-peptidaseC28.002-
family C28 non-peptidase homologuesnon-peptidase homologue-
family C28 unassigned peptidasesunassigned-