PPIase

PPIase, or peptidyl-prolyl cis-trans isomerase, is a class of enzymes that catalyze the cis-trans isomerization of peptide bonds preceding proline residues in polypeptides. This reaction toggles between proline’s cis and trans conformations, a rate-limiting step in protein folding, enabling faster folding, conformational switching, and signal transduction.

PPIases are grouped into several families based on sequence and structural similarities: cyclophilins, FK506-binding proteins (FKBPs), and parvulins. Cyclophilins, which include cyclophilin A, bind the immunosuppressant cyclosporin A. FKBPs bind tacrolimus (FK506) and diverse ligands. Parvulins, such as Pin1, have distinct substrate specificities and regulate signaling pathways through cis-trans isomerization of specific proline-containing motifs. Many organisms encode multiple PPIases, with localization ranging from cytosol and nucleus to mitochondria and chloroplasts; bacteria may secrete periplasmic forms.

Functionally, PPIases act as chaperones and accelerators of protein folding, contributing to proper folding, maturation, and sometimes conformational changes that regulate activity. In addition to their catalytic role, some PPIases participate in signaling networks or act as scaffolds. Their activity can be independent of ligand binding and can influence protein stability and interactions.

Because of their central role in protein folding and signaling, PPIases are important in biology and medicine. Immunosuppressive drugs such as cyclosporin A and tacrolimus exert effects by inhibiting PPIase–ligand interactions in immune cells, illustrating the therapeutic relevance of this enzyme class.