Peptidylprolyl

Peptidylprolyl refers to the peptidyl bond preceding a proline residue in proteins, the X-Pro bond, and, more broadly, to enzymes and reactions that act on this bond. The most studied activity is peptidyl-prolyl cis-trans isomerization, which interconverts the cis and trans configurations of X-Pro peptide bonds and is often a rate-limiting step in protein folding and conformational change.

Enzymes that catalyze this reaction are peptidyl-prolyl cis-trans isomerases (PPIases). They accelerate isomerization by stabilizing the transition state. Three major families are recognized: cyclophilins, FK506-binding proteins (FKBPs), and parvulins. Cyclophilins (e.g., cyclophilin A) and FKBPs (e.g., FKBP12) are notable for binding small molecule immunosuppressants such as cyclosporin A and tacrolimus, respectively, which can inhibit downstream signaling pathways. Parvulins, including Pin1, differ in substrate specificity: Pin1 preferentially recognizes phospho-Ser/Thr-Pro motifs and links isomerization to signal transduction and cell-cycle control.

Biological roles include assisting protein folding, regulating protein function through conformational changes, and influencing protein trafficking and complex assembly. Because the X-Pro bond frequently affects structural dynamics, PPIases participate in diverse processes from immunity to neurobiology. Dysregulation of PPIase activity has been associated with diseases such as cancer and neurodegenerative disorders, making them subjects of therapeutic interest.

In summary, peptidylprolyl concerns the bonds around proline and the enzymes that modulate them, which are essential for proper protein folding and function.