Family C28
Summary for family C28
Family type peptidase | C28.001 - foot-and-mouth disease virus L-peptidase (foot-and-mouth disease virus), MEROPS Accession MER0002022 (peptidase unit: 1-201) |
Content of family | Peptidase 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 type | Cysteine |
Active site residues | N47 C51 H148 D163 |
Active site | The active site residues are in the order Asn, Cys, His, Asp. |
Activities and specificities | The 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. |
Inhibitors | Both the cleavage of eIF-4G and the L-VP4 scissile bond are inhibited by E-64d in infected cells (Kleina & Grubman, 1992). |
Molecular structure | The 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. |
Clan | CA |
Basis of clan assignment | Protein fold of the peptidase unit for members of this family and resembles that of papain, the type example for clan CA. |
Distribution of family
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Bacteria |
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Archaea |
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Protozoa |
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Fungi |
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Plants |
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Animals |
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Viruses |
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Biological functions | The 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 C28 | Sequences: | 29 |
| Identifiers: | 2 |
| Identifiers with PDB entries: | 1 |
Downloadable files |
Sequence library (FastA format) |
| Sequence alignment (FastA format) |
| Phylogenetic tree (Newick format) |