Family C60
Summary for family C60
| Family type peptidase | C60.001 - sortase A (Staphylococcus-type) (Staphylococcus aureus), MEROPS Accession MER0018290 (peptidase unit: 1-206) |
| Content of family | Peptidase family C60 contains bacterial peptidases with strong transferase activity. |
| History |
Identifier created: MEROPS 6.1 (10 January 2003)
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| Catalytic type | Cysteine |
| Active site | Residues essential for activity include His120 and Cys184 (see the Alignment), but the two residues probably do not form an ion-pair (Connolly et al., 2003). A third active site residue may be Arg197 (Marraffini et al., 2004; Zong et al., 2004). |
| Activities and specificities | Sortase A (C60.001) cleaves proteins in the LPXT G motif, and then catalyzes the formation of an amide bond between the new C-terminal Thr and a cell wall pentaglycine cross-bridge (Zong et al., 2004). Specificity for the acceptor requires Gly in P1", and prefers Gly in P2" (Huang et al., 2003). Sortase B (C60.002) catalyses a similar reaction, but the consensus cleavage site is NPQTN (Mazmanian et al., 2002). Substrate specificities of many forms of sortase have been described in detail by Comfort & Clubb, 2004. In vitro, an acceptor such as Gly-Gly-Gly can substitute for the natural acceptor, and in the absence of an acceptor hydrolysis take place (Kruger et al., 2004). |
| Inhibitors | Sortases are inhibited by compound E-64 (Zong et al., 2004), and also by peptidyl diazomethanes containing the Leu-Pro-Ala-Thr recognition sequence (Scott et al., 2002). Other classes of inhibitors include vinyl sulfones and diarylacrylonitriles (Connolly et al., 2003; Oh et al., 2004). |
| Molecular structure | Structures described for both sortase A and sortase B show a protein fold that had not been seen for any other peptidase, and the sortase A fold is the type structure for clan CL. The core of the protein is an eight-stranded beta-barrel with mainly antiparallel strands that is decorated by five alpha-helices (Zong et al., 2004; Zhang et al., 2004). |
| Clan | CL |
| Basis of clan assignment | Type family of clan CL. |
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Distribution of family
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Bacteria |
details |
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Archaea |
details |
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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 |
details |
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| Biological functions | The sortases covalently attach a variety of proteins to the exterior of the bacterial cell wall. These proteins include some that contribute to the diseases caused by the pathogenic bacteria involved. |
| Pharmaceutical and biotech relevance | There is evidence that inhibition of sortase activity might decrease the virulence of some pathogenic bacteria, so sortases are regarded as targets for antibacterial drugs. |
| Statistics for family C60 | Sequences: | 1919 |
| Identifiers: | 9 |
| Identifiers with PDB entries: | 6 |
| Downloadable files |
Sequence library (FastA format) |
| Sequence alignment (FastA format) |
| Phylogenetic tree (Newick format) |
| Peptidases and Homologues |
MEROPS ID |
Structure |
| sortase B | C60.002 | Yes |
| sortase C2 | C60.003 | Yes |
| Subfamily C60B unassigned peptidases | unassigned | - |
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Peptidases not assigned to subfamily
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