Family S32


Summary Holotypes Alignment Tree Genomes Structure Literature

Summary for family S32

Family type peptidaseS32.001 - equine arteritis virus serine peptidase (equine arteritis virus), MEROPS Accession MER0000304 (peptidase unit: 1065-1261)
Content of familyPeptidase family S32 contains one of the arterivirus polyprotein processing endopeptidases.
History Identifier created: Methods Enzymol. 244:19-61 (1994)
Arteriviruses are RNA viruses with a genome that encodes two polyproteins, ORF1a and ORF1ab. ORF1ab is the result of a ribosomal frameshift. Both polyproteins are processed by endopeptidases that are components of the polyproteins. In equine arteritis virus there are two cysteine endopeptidases (see families C32 and C33) and the serine endopeptidase S32.001 (also known as non-structural protein 4, Nsp4). Other arteriviruses have a third cysteine endopeptidase (see family C31), but in equine arteritis virus this has been inactivated by a mutation in one of the active site residues.
Catalytic typeSerine
Active site residuesH1103 D1129 S1184 
Active siteActive site residues occur in the order His, Asp, Ser in the sequence (see the Alignment).
Activities and specificitiesCleavage occurs at four GluGly bonds and one GluSer bond in the ORF1a polyprotein, and an additional two GluGly and one GlnSer bond in the ORF1b polyprotein (Van Dinten et al., 1999). Because of this specificity, which is similar to that of picornain 3C (C03.001), peptidases in family S32 have been described as '3C-like'. Selectivity is thought to be determined by Thr1179 and His1198 (see the Alignment), which are proposed to occupy the substrate-binding region. Some molecules show a collapsed, inactive conformation of the oxyanion hole and it has been suggested that this is a novel mechanism by which activity is controlled (Barrette-Ng et al., 2002).
Molecular structureThe tertiary structure has been determined by Barrette-Ng et al., 2002, and shows a fold similar to that of chymotrypsin (S01.001); hence family S32 is included in clan PA. There is an additional C-terminal domain of unknown function.
Basis of clan assignmentActive site residues for members of this family and family S1 occur in the same order in the sequence: H, D, S.
Distribution of family Bacteria -  
Archaea -  
Protozoa -  
Fungi -  
Plants -  
Animals -  
Viruses details  
Biological functionsProcessing of the polyproteins by the cysteine endopeptidases is an essential preliminary to cleavage by Nsp4. The Nsp2 protein is an essential cofactor for cleavage between the Nsp4 and Nsp5 proteins and without it Nsp4 cleaves the bonds between Nsp5 and Nsp6 and between Nsp6 and Nsp7, instead (Wassenaar et al., 1997).
Pharmaceutical and biotech relevanceEquine arteritis virus causes an economically important disease of racehorses, and because disruption of the Nsp4 cleavage sites by mutagenesis blocks virus replication (Van Dinten et al., 1999) the Nsp4 peptidase is a potential drug target.
Statistics for family S32Sequences:31
Identifiers with PDB entries:2
Downloadable files Sequence library (FastA format)
Sequence alignment (FastA format)
Phylogenetic tree (Newick format)
Peptidases and Homologues MEROPS ID Structure
equine arteritis virus serine peptidaseS32.001Yes
porcine reproductive and respiratory syndrome virus nsp4 peptidaseS32.002Yes
family S32 unassigned peptidasesunassigned-