Prolyl Isomerases as Tools in Protein Folding

The characterization of the molecular nature of rate-limiting steps is a major aim in the elucidation of the folding mechanism of proteins. It is now clear that cis—trans isomerizations of prolyl peptide bonds can be such slow steps. Folding reactions that involve prolyl isomerization were traditionally identified by measuring their kinetic properties and by comparing them with the properties of prolyl isomerization in short peptides (Brandts et ai, 1975 Nall et al., 1978 Schmid and Baldwin, 1978). 

Prolyl isomerizations have the following characteristic properties  

PPIs with increasing concentration of denaturant. A significant inhibition is observed for the enzymes from porcine kidney and from E. coli already in the presence of less than 0.5 M urea or GdmCl. 

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