Peptidylprolyl isomerase A (PPIA)

Peptidylprolyl isomerase A (PPIA, cyclophilin A) is a cytosolic enzyme of 165 amino acids, crucial for protein folding due to its ability to catalyze cis-trans isomerization of proline imidic peptide bonds. This activity impacts intracellular signaling, transcription, apoptosis, and inflammation. Cyclosporine is a key inhibitor, forming a complex that blocks its function, underlying the therapeutic use of cyclophilin-targeting drugs for immunosuppression in transplant patients and autoimmune diseases. Dysregulation or altered activity of PPIA is implicated in atherosclerosis, arthritis, several viral infections, and as a mediator in cancer-related pathways, making it an extensively studied drug target.

Other names

Cyclophilin ACypARotamase A

Inhibition of enzymatic activity: Cyclosporine binds the hydrophobic pocket of cyclophilin A and inhibits its peptidyl-prolyl isomerase activity, thereby blocking processes like protein folding and subsequent immune signaling. Sequestration of calcineurin (through complex formation with cyclophilin-cyclosporine complex, leading to immune suppression).