Peptidyl-prolyl cis-trans isomerase A (PPIA) (PPIA)

Peptidyl-prolyl cis-trans isomerase A (PPIA), also known as rotamase A or cyclophilin A, is a periplasmic enzyme in Escherichia coli K12 that facilitates the interconversion of cis and trans isomers of proline peptide bonds (UniProt P0AFL3; EcoCyc G7241). This catalytic activity is a rate-limiting step in protein folding, making PPIA essential for the rapid maturation of various proteins, particularly those translocated to the periplasm (UniProt P0AFL3). While PPIA is not strictly essential for bacterial viability under standard conditions, it contributes to the bacterial stress response and the proper assembly of cell envelope components (EcoCyc G7241). In the field of drug discovery, bacterial PPIases are explored as potential targets for novel antimicrobial agents designed to disrupt protein homeostasis and virulence (PMID: 24713330). However, therapeutic development is complicated by the high structural similarity between bacterial PPIA and human cyclophilin A, which is the primary target of the immunosuppressant drug Cyclosporine A (PMID: 2623557).

Other names

Cyclophilin ARotamase AppiArotAPPIase APeptidyl-prolyl cis-trans isomerase A homolog

Competitive inhibition of the peptidyl-prolyl isomerase active site, which prevents the proper folding of proline-containing proteins and disrupts bacterial cellular processes (PMID: 1707554).