Prolyl Isomerases as Catalysts of in Vitro Protein Folding

Prolyl Isomerases as Catalysts of in Vitro Protein Folding 

The first evidence for a catalysis of protein folding by a prolyl isomerase (porcine cytoplasmic Cypl8) came from experiments with the 

In the maturation of the collagen triple helix, prolyl and hydroxyprolyl isomerizations are rate-limiting steps (Bachinger et al., 1980 Buevich et al., 2000) and accelerated by Cypl8 (Bachinger, 1987 Davis et al., 1989). For mouse dihydrofolate reductase, the overall formation of the catalytically active protein is accelerated by cyclophilin, but it is not the 

Prolyl isomerases are enzymes. In protein folding they catalyze cis trans isomerizations in both directions (Miicke and Schmid, 1992) and show equal efficiencies in unfolding and refolding experiments under identical conditions near the midpoint of the unfolding transition. They carry no information about the isomeric states of the prolyl peptide bonds in the protein substrates. The native isomer is selected by the refolding protein itself simply because the molecules 

The prolyl isomerases catalyze isomerizations only at prolyl bonds and not at nonprolyl peptide bonds. The refolding of the P39A variant of RNase Tl, which is limited in rate by the very slow trans — cis reisomerization of the Tyr38-Ala39 bond (see Section IV.B), is not catalyzed by cyclophilins, FKBPs, or parvulins. These enzymes are also unable to catalyze amide bond isomerizations in the proline-free model peptide Ala-Ala-Tyr-Ala-Ala (Scholz etal., 1998b). 

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VIII. Prolyl Isomerases as Catalysts of in Vitro Protein Folding. 261... 

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