Sortase

Sortase

Sortase is a family of bacterial enzymes that play a crucial role in the post-translational modification of proteins. These enzymes are primarily responsible for anchoring surface proteins to the cell wall of Gram-positive bacteria, a process that is essential for bacterial virulence and colonization.

Structure and Mechanism

Sortases are cysteine transpeptidases that recognize and cleave specific peptide motifs, typically the LPXTG motif, where X can be any amino acid. The enzyme cleaves between the threonine and glycine residues, forming an acyl-enzyme intermediate. This intermediate is then resolved by the nucleophilic attack of an amino group from the cell wall peptidoglycan precursor, resulting in the covalent attachment of the protein to the cell wall.

Active Site

The active site of sortase enzymes contains a catalytic triad composed of cysteine, histidine, and arginine residues. These residues are crucial for the enzyme's catalytic activity, facilitating the cleavage and transpeptidation reactions.

Biological Function

Sortases are essential for the pathogenesis of many Gram-positive bacteria, including Staphylococcus aureus, Streptococcus pyogenes, and Listeria monocytogenes. By anchoring virulence factors to the bacterial surface, sortases enable these pathogens to adhere to host tissues, evade the immune system, and establish infections.

Applications in Biotechnology

Due to their ability to catalyze site-specific protein modifications, sortases have been harnessed in various biotechnological applications. These include protein engineering, the development of novel therapeutics, and the creation of protein-based materials. Sortase-mediated ligation is a powerful tool for the site-specific conjugation of proteins, peptides, and other biomolecules.

Sortase Inhibitors

Given their role in bacterial virulence, sortases are attractive targets for the development of new antimicrobial agents. Sortase inhibitors have the potential to disarm pathogenic bacteria by preventing the anchoring of virulence factors, thereby reducing their ability to cause disease.

Also see

• Transpeptidase
• Gram-positive bacteria
• Protein engineering
• Bacterial virulence factors