Prolyl isomerase

Peptidyl- prolyl cis -trans isomerases ( PPIases also or PPIs) are enzymes that are found in all living things. To catalyze the bond axes of rotation of amide bonds in proteins in which the amino acid proline is involved. This reaction is the rate-limiting step in protein folding. In humans, at least 33 different PPIases are known, of which several are already the target of active pharmaceutical ingredients.

PPIases are divided into three classes: the cyclophilins, FK506 -binding proteins and parvulins.

Protein Folding

Amide bonds in peptides and proteins are able to rotate freely and quickly, in most cases, an exception to the bonds between the N-terminus of proline, and the C-terminus of another amino acid. This bond can be present both in the trans and in the cis configuration, a change between the two configurations only takes place slowly. This is due to the cyclic structure of the proline molecule in which the amino group adjacent to the central C - atom ( α -C - atom ) is connected to the side chain of the amino acid, which is the case for any other proteinogenic amino acid.

The specific protein folding ( formation of the three-dimensional structure) of such proteins, which depends among other things on the spatial structures of the individual bonds, therefore, can not automatically occur spontaneously. The peptidyl- prolyl cis -trans isomerases act here as chaperones ( they are among the chaperones ). The enzymes are able to switch between the cis and the trans configuration of the respective peptide bond, so that the protein can fold correctly and only then perform its function. This can result in both cis -and trans - configurations.