Family C30

Family

Summary Holotypes Alignment Tree Genomes Structure Literature Architecture

Summary for family C30

Family type peptidase	C30.004 - porcine transmissible gastroenteritis virus-type main peptidase (transmissible gastroenteritis virus), MEROPS Accession MER0002860 (peptidase unit: 2879-3180)
Content of family	Family C30 contains endopeptidases from coronaviruses.
History	Identifier created: Perspect.Drug Discov.Des. 6:1-11 (1996) Following the study of the murine hepatitis coronavirus genome (Lee et al., 1991) it has become clear that the coronaviruses encode picornain-like peptidases (family C30, clan PA) and commonly also papain-like peptidases (family C16, clan CA).
Catalytic type	Cysteine
Active site residues	H2919 C3022
Active site	The active site residues of the peptidases of family C30 are a His and a Cys, which form a catalytic dyad (see the Alignment).
Activities and specificities	Endopeptidases of family C30 are polyprotein processing. The specificity of the 3C-like peptidase is highly conserved among coronaviruses (Ziebuhr et al., 2000; Hegyi & Ziebuhr, 2002). There is a requirement for Gln at position P1 (Tibbles et al., 1996), whilst P1" may be occupied by small aliphatic residues. At position P2 Leu is usually found, but may be Ile, Tyr, Val, Phe or Met. P4 may contain Val, Ala, Ser or Tyr.
Inhibitors	The most detailed information about inhibitors of family C30 peptidases relates to the peptidase (C30.005) of the SARS coronavirus. This is a major drug target, and work towards inhibitors that could have therapeutic use has been reviewed by Liang (2006).
Molecular structure	As can be seen from the Structure pages for C30.003, C30.004 and C30.005, the tertiary structures of peptidases in family C30 consist of three domains. The first two contain anti-parallel beta barrels, with the third consisting of an arrangement of alpha-helices. The catalytic residues are found in a cleft between the first two domains. This structure is characteristic of clan PA.
Clan	PA
Subclan	PA(C)
Basis of clan assignment	Active site residues for members of this family and family S1 occur in the same order in the sequence: H, C/S.

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

Biological functions	During viral replication, the viral peptidases, polymerase and helicase of the coronavirus are expressed as a polyprotein with a number of putative picornain 3C-like endopeptidase cleavage sites. Processing of the polyprotein by 3C-like endopeptidase liberates active forms of the viral replicase proteins. Processing is required throughout the infection cycle, and therefore, the role of 3C-like endopeptidase is critical in viral replication (Kim et al., 1995).
Pharmaceutical and biotech relevance	The SARS virus 3C-like endopeptidase (C30.005) is a target for the treatment of severe acute respiratory syndrome (SARS).
Reviews	Ziebuhr et al. (2000); Denison (2004)
Statistics for family C30	Sequences:	99
	Identifiers:	7
	Identifiers with PDB entries:	7
Downloadable files	Sequence library (FastA format)
	Sequence alignment (FastA format)
	Phylogenetic tree (Newick format)

Other databases	CATH	1.10.1840.10
	INTERPRO	IPR008740
	PFAM	PF05409
	SCOP	50603

Peptidases and Homologues	MEROPS ID	Structure
coronavirus picornain 3C-like peptidase-1	C30.001	Yes
avian infectious bronchitis coronavirus 3C-like peptidase	C30.002	Yes
human coronavirus 229E main peptidase	C30.003	Yes
porcine transmissible gastroenteritis virus-type main peptidase	C30.004	Yes
SARS coronavirus picornain 3C-like peptidase	C30.005	Yes
MERS coronavirus picornain 3C-like peptidase	C30.006	Yes
coronavirus COVID-19 3C-like peptidase	C30.007	-
Family C30 unassigned peptidases	unassigned	Yes