For most substrates of sortase enzymes, the recognition signal consists of the motif LPXTG (Leu-Pro-any-Thr-Gly), then a highly hydrophobic transmembrane sequence, followed by a cluster of basic residues such as arginine.

Sortases occur in almost all Gram-positive bacteria and the occasional Gram-negative bacterium (e.g. Shewanella putrefaciens) or Archaea (e.g. Methanobacterium thermoautotrophicum), where cell wall LPXTG-mediated decoration has not been reported.

[4][5][6] The Staphylococcus aureus sortase is a transpeptidase that attaches surface proteins to the cell wall; it cleaves between the Gly and Thr of the LPXTG motif and catalyses the formation of an amide bond between the carboxyl-group of threonine and the amino-group of the cell-wall peptidoglycan.

[7][8] Substrate proteins attached to cell walls by sortases include enzymes, pilins, and adhesion-mediating large surface glycoproteins.

Surface proteins not only promote interaction between the invading pathogen and animal tissues, but also provide ingenious strategies for bacterial escape from the host's immune response.

S. aureus mutants lacking the srtA gene fail to anchor and display some surface proteins and are impaired in the ability to cause animal infections.

[9] The sortases are thought to be good targets for new antibiotics[10] as they are important proteins for pathogenic bacteria and some limited commercial interest has been noted by at least one company.

The most widely used sortase in biological and medical applications is the SrtA enzyme found in staphylococcus aureus bacteria, which recognizes an LPXTG binding motif.