Peptidyl prolyl cis/trans isomerases PPIases

Peptidyl prolyl cis-trans isomerases (PPIases) are able to catalyze the folding or unfolding reaction. 

Conformational restriction played an important role in the discovery that water induces the bioactive conformation of CsA. Cyclosporin A (Sandimmune , CsA, (23.37), Fig. 23.7), is a major drug for preventing rejection of transplanted human organs and has been the subject of many synthetic, conformational and mechanism of action studies. To produce immunosuppression, CsA first binds to cyclophilin A (CyP A), a peptidyl prolyl cis-trans isomerase (PPIase), to form the CsA-CyP complex, which then binds to and inhibits calcineuiin (CaN), a calmodulin-dependent serine/threonine protein phosphatase, thereby inhibiting interleukin-2 (IL-2) synthesis. ... 

The essential lipoprotein PrsA, which localizes to the outer surface of the cytoplasmic membrane (Figure 7.1), can also be used to enhance secretion of particular proteins [65]. PrsA belongs to the parvulin subfamily of peptidyl-prolyl cis/trans isomerases (PPIases) [66]. The PPIase domain of PrsA exhibits PPIase activity and a possible chaperone activity in vivo at the membrane-cell wall interface [65]. Overexpression of PrsA was shown to enhance the secretion of several extracellular proteins, including a-amylases [57,65]. Furthermore, PrsA overproduction in B. subtilis resulted in 1.5-fold increased secretion and activity of the pharmacologically relevant human interferon-fi (hlNF-fi) with the AmyE propeptide [67]. 

Beyond protein folding, the discovery of peptidyl prolyl isomerases (PPIases) and related proteins has opened the way to novel concepts in biology the notion of chaperone-assisted receptor binding is an emerging field of research which sheds light on receptor function and protein-protein interactions. The recent discovery of a secondary amide peptide bond cis-trans isomerase (APIase) heralds new advances in this field. 

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