Family C57

Family

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Summary for family C57

Name	Peptidase family C57 (vaccinia virus I7 peptidase family)
Family type peptidase	C57.001 - vaccinia virus I7L processing peptidase (Vaccinia virus), MEROPS Accession MER0013959 (peptidase unit: 1-423)
Content of family	Peptidase family C57 contains endopeptidases that process the precursors of viral proteins.
History	Identifier created: MEROPS 5.4 (23 March 2001) The family Poxviridae includes double-stranded DNA viruses such as vaccinia and variola (smallpox) viruses. Poxviruses do not encode a polyprotein, but instead have a gene for each protein. Some of these proteins are synthesized as precursors, and the product of the I7L viral gene has been shown to be the endopeptidase responsible for their activation. In addition to the I7L protein, the vaccinia virus genome encodes a metallopeptidase (see M44.001).
Catalytic type	Cysteine
Active site residues	H241 D,N258 Q322 C328
Active site	The active site triad (His, Asp, Cys) has been identified by site-directed mutagenesis (Byrd et al., 2002). By analogy with other members of clan CE, a glutamine is predicted to be important for formation of the oxyanion hole (Byrd et al., 2004).
Activities and specificities	The P4b and P25K proteins are cleaved within an Ala-Gly-Ala motif (VanSlyke et al., 1991). The P4a precursor is also cleaved but at Ala-GlySer (Byrd et al., 2003. At a later stage in viral maturation, the precursor of the IMV membrane protein is processed at Ala-GlyAsn (Ansarah-Sobrinho & Moss, 2004).
Inhibitors	Vaccinia virus replication has been shown to be inhibited by 10 μM iodoacetamide and 1 μM 1,10-phenanthroline, consistent with the hypothesis that a cysteine peptidase and a metallopeptidase are essential (Byrd et al., 2002; Ansarah-Sobrinho & Moss, 2004). An inhibitor of the I7L peptidase known as TTP-6171 has been described (Byrd et al., 2004).
Molecular structure	In the absence of a tertiary structure, family C57 is included in clan CE on the basis of the order of active site residues. The structure has been modelled on the basis of Ulp1 peptidase (C48.001) by Byrd et al. (2004).
Clan	CE
Basis of clan assignment	Predicted active site residues for members of this family and family C5 occur in the same order in the sequence: H, D/E, Q, C.

Distribution of family	Bacteria	-
	Archaea	-
	Protozoa	-
	Fungi	-
	Plants	-
	Animals	-
	Viruses	details

Biological functions	The I7L peptidase processes the precursors of three of the most abundant proteins in the vaccinia virus particle, the major core proteins 4a, 4b and 25K (encoded by the genes A10L, A3L and L4R, respectively). It also processes the IMV membrane protein (encoded by the gene A17L).
Pharmaceutical and biotech relevance	Vaccinia virus has been widely used in vaccinations against smallpox and is being investigated for use as a vector in vaccinations against other viral diseases. Vaccinia virus is not itself pathogenic. The drug rifampin inhibits processing of the core proteins during the early stage of virus maturation (Moss & Rosenblum, 1973, but does not affect later processing of the A17 and L4 proteins (Ansarah-Sobrinho & Moss, 2004).
Reviews	Byrd et al. (2004)
Statistics for family C57	Sequences:	34
	Identifiers:	1
	Identifiers with PDB entries:	0
Downloadable files	Sequence library (FastA format)
	Sequence alignment (FastA format)
	Phylogenetic tree (Newick format)

Other databases	INTERPRO	IPR004970
	PFAM	PF03290

Peptidases and Homologues	MEROPS ID	Structure
vaccinia virus I7L processing peptidase	C57.001	-
Family C57 unassigned peptidases	unassigned	-