Family C3
Summary for family C3
| Name | Peptidase family C3 (picornain family) |
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| Family type peptidase | C03.001 - poliovirus-type picornain 3C (human poliovirus 1), MEROPS Accession MER0000748 (peptidase unit: 1564-1745) |
| Content of family | Peptidase family C3 contains processing endopeptidases of RNA viruses. |
| History |
Identifier created: Biochem.J. 290:205-218 (1993)
In the mid-1980"s, the surprising discovery was made that the 3C processing peptidases of poliovirus and other picornaviruses have some similarities in sequence to chymotrypsin and its relatives (Bazan & Fletterick, 1988; Gorbalenya et al., 1989). The relationship was confirmed by the crystallographic structure of picornain 3C from human hepatitis A virus (e.g. Matthews et al., 1994). This was the first indication that a peptidase of one catalytic type can evolve into one of another, and led to the creation of clan PA in MEROPS. (The 'P' in the clan identifier indicates that this is a clan containing mixed types of Protein nucleophile peptidase families.) |
| Catalytic type | Cysteine |
| Active site | Confirmed catalytic residues are His1603 and Cys1710 (see the Alignment). Asp1634 is close to the position expected for the third member of a catalytic triad analogous to those in family S1. In the hepatitis A virus enzyme it is unlikely to fill this role because the orientation of its side chain in the crystal structure is not as expected, and an ordered water molecule occupies the position of the carboxylate of the third member of a typical catalytic triad (Bergmann, 2004). |
| Activities and specificities | Bonds cleaved in processing the viral polyprotein are commonly -Gln Gly-. A biologically-significant substrate in addition to the viral polyprotein is the eukaryotic initiation factor 4G (Foeger et al., 2003). Cleavage of eIF4G probably contributes to the viral takeover of protein synthesis in the host cell. |
| Inhibitors | Many synthetic inhibitors have been designed as possible leads to antiviral drugs; the structures of these commonly mimic glutamine (e.g. Ramtohul et al., 2002). |
| Molecular structure | The predominant feature of the protein folds of the peptidases in family C3, in common with others in clan PA, is a pair of beta-barrels ar right-angles, with the catalytic residues between them. |
| Clan | PA |
| Subclan | PA(C) |
| Basis of clan assignment | Protein fold of the peptidase unit for members of this family resembles that of chymotrypsin, the type example for clan PA. |
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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 picornains are components of the polyproteins of small RNA viruses of the Picornaviridae group (picornaviruses, aphthoviruses, nepoviruses and comoviruses). Maturation of the viruses requires the processing of the polyproteins that is commonly mediated by endopeptidases of family C3. |
| Pharmaceutical and biotech relevance | The enzymes are potential targets for antiviral drugs. Among the many diseases that might be tackled in this way are poliomyelitis, the common cold, hepatitis A and foot-and-mouth disease. |
| Statistics for family C3 | Sequences: | 1136 |
| Identifiers: | 19 |
| Identifiers with PDB entries: | 12 |
| Downloadable files |
Sequence library (FastA format) |
| Sequence alignment (FastA format) |
| Phylogenetic tree (Newick format) |
| Peptidases and Homologues |
MEROPS ID |
Structure |
| poliovirus-type picornain 3C | C03.001 | Yes |
| human rhinovirus 2-type picornain 3C | C03.007 | Yes |
| Coxsackievirus-type picornain 3C | C03.011 | Yes |
| human rhinovirus 14-type 3C peptidase | C03.013 | - |
| human enterovirus 71 3C peptidase | C03.014 | Yes |
| Subfamily C3A non-peptidase homologues | non-peptidase homologue | Yes |
| Subfamily C3A unassigned peptidases | unassigned | Yes |
| Peptidases and Homologues |
MEROPS ID |
Structure |
| foot-and-mouth disease virus picornain 3C | C03.008 | Yes |
| cardiovirus picornain 3C | C03.009 | - |
| Theiler's murine encephalomyelitis virus picornain 3C | C03.010 | - |
| Subfamily C3C non-peptidase homologues | non-peptidase homologue | - |
| Subfamily C3C unassigned peptidases | unassigned | Yes |
| Peptidases and Homologues |
MEROPS ID |
Structure |
| cowpea mosaic comovirus-type picornain 3C | C03.003 | - |
| Subfamily C3D non-peptidase homologues | non-peptidase homologue | - |
| Subfamily C3D unassigned peptidases | unassigned | - |
| Peptidases and Homologues |
MEROPS ID |
Structure |
| hepatitis A virus-type picornain 3C | C03.005 | Yes |
| Subfamily C3E unassigned peptidases | unassigned | - |
| Peptidases and Homologues |
MEROPS ID |
Structure |
| Plautia stali intestine virus picornain C3 | C03.015 | - |
| tomato marchitez virus 3C peptidase | C03.016 | - |
| rice tungro spherical virus-type peptidase | C03.024 | - |
| Subfamily C3G non-peptidase homologues | non-peptidase homologue | - |
| Subfamily C3G unassigned peptidases | unassigned | - |
| Peptidases and Homologues |
MEROPS ID |
Structure |
| grapevine fanleaf-type nepovirus picornain 3C | C03.004 | - |
| tomato black ring virus-type picornain | C03.025 | - |
| Subfamily C3H unassigned peptidases | unassigned | - |
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Peptidases not assigned to subfamily
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