Family C16

Family

Summary Holotypes Alignment Tree Genomes Structure Literature

C16A

Summary Holotypes Alignment Tree Genomes Literature

C16B

Summary Holotypes Alignment Tree Genomes Literature

Summary for family C16

Family type peptidaseC16.001 - murine hepatitis coronavirus papain-like peptidase 1 (murine hepatitis virus), MEROPS Accession MER0000859 (peptidase unit: 1083-1332)
Content of familyPeptidase family C16 contains polyprotein processing endopeptidases from coronaviruses.
History Identifier created: Methods Enzymol. 244:461-486 (1994)
The murine hepatitis coronavirus genome contains one large polyprotein. The polyprotein gene is ORF1 and because of a ribosomal frameshift it can be translated as an ORF1a or ORF1b polyprotein. The polyprotein is processed to fifteen proteins, including an RNA-directed RNA polymerase, a helicase and three endopeptidases. Papain-like proteinase 1 (PLP1; C16.001) and papain-like proteinase 2 (PLP2, C16.006) are both members of family C16, whereas the 3C-like proteinase is a member of family C30.
Catalytic typeCysteine
Active siteA catalytic triad, Cys, His, Asp has been demonstrated in the SARS coronavirus papain-like peptidase (C16.009) both by site-directed mutagenesis (Barretto et al., 2005) and X-ray crystallography (Ratia et al., 2006), and this is present throughout the family (see the Alignment).
Activities and specificitiesBoth PLP1 and PLP2 have restricted specificities, cleaving only two and one bond(s) in the polyprotein, respectively. The restricted activity may be due to extended specificity sites: a requirement for Arg or Lys in P5 has been shown for PLP1 (Dong & Baker, 1994), and a requirement for Phe in P6 in PLP2 (Kanjanahaluethai & Baker, 2003).
InhibitorsNo potent inhibitors of the peptidases in family C16 have been described, but there are indications of weak inhibition by leupeptin, E-64d or loxistatin and Zn2+ (reviewed by Kanjanahaluethai & Baker, 2004). There may also be inhibition by ubiquitin aldehyde (Ratia et al., 2006).
Molecular structureThe structure of the SARS coronavirus papain-like peptidase (C16.009) confirms the place of family C16 in clan CA, and shows the closest similarity to deubiquitinating peptidases in family C19 (Ratia et al., 2006). Binding sites for ubiquitin and zinc are present.
ClanCA
Basis of clan assignmentActive site residues for members of this family and family C1 occur in the same order in the sequence: C, H.
Distribution of family Bacteria -  
Archaea -  
Protozoa -  
Fungi -  
Plants -  
Animals -  
Viruses details  
Biological functionsPLP1 releases proteins p28 and p65 from the N-terminus of the polyprotein; PLP2 cleaves between proteins p210 and p150.
Pharmaceutical and biotech relevanceCoronaviruses cause respiratory infections, including severe acute respiratory syndrome (SARS). The polyprotein processing peptidases are potential drug targets, although most research has been focussed on the 3C-like proteinases, especially in the SARS coronavirus.
ReviewsKanjanahaluethai & Baker (2004); Ratia et al. (2006)
Statistics for family C16Sequences:73
Identifiers:10
Identifiers with PDB entries:3
Downloadable files Sequence library (FastA format)
Sequence alignment (FastA format)
Phylogenetic tree (Newick format)
Subfamily C16A
Name Peptidase subfamily C16A
Subfamily type peptidase C16.001 - murine hepatitis coronavirus papain-like peptidase 1 (murine hepatitis virus), MEROPS Accession MER0000859 (peptidase unit: 1083-1332)
Active site residues C1120 H1271 D1282 
Statistics Sequences: 5
Identifiers: 1
Identifiers with PDB entries: 0
Other databases INTERPRO IPR002705
PFAM PF01831
Downloadable files Sequence library [FastA format]
Sequence alignment [FastA format]
Phylogenetic tree [Newick format]
Peptidases and Homologues MEROPS ID Structure
murine hepatitis coronavirus papain-like peptidase 1C16.001-
subfamily C16A non-peptidase homologuesnon-peptidase homologue-
subfamily C16A unassigned peptidasesunassigned-
Subfamily C16B
Name Peptidase subfamily C16B
Subfamily type peptidase C16.006 - murine hepatitis coronavirus papain-like peptidase 2 (murine hepatitis virus), MEROPS Accession MER0002028 (peptidase unit: 1679-1936)
Active site residues C1715 H1872 D1886 
Statistics Sequences: 70
Identifiers: 9
Identifiers with PDB entries: 3
Other databases PFAM PF08715
SCOP 50603
Downloadable files Sequence library [FastA format]
Sequence alignment [FastA format]
Phylogenetic tree [Newick format]
Peptidases and Homologues MEROPS ID Structure
human coronavirus 229E papain-like peptidase 1C16.002-
porcine epidemic diarrhea virus papain-like peptidase 1C16.003-
porcine transmissible gastroenteritis coronavirus papain-like peptidase 1C16.004-
avian infectious bronchitis coronavirus papain-like peptidaseC16.005Yes
murine hepatitis coronavirus papain-like peptidase 2C16.006-
porcine transmissible gastroenteritis coronavirus papain-like peptidase 2C16.008-
severe acute respiratory syndrome coronavirus papain-like peptidaseC16.009Yes
human coronavirus 229E papain-like peptidase 2C16.010-
Middle East respiratory syndrome coronavirus papain-like peptidaseC16.011Yes
non-peptidase homologue-
subfamily C16B unassigned peptidasesunassigned-