PROLYL ISOMERASES DO NOT CATALYZE ISOMERIZATION OF NON-PROLYL PEPTIDE-BONDS

Prolyl isomerases accelerate the cis reversible arrow trans isomerizat ion of prolyl peptide bonds during protein folding and probably also i n folded proteins. We asked whether this catalytic function is in fact restricted to prolyl bonds or whether the isomerizations of 'normal' non-prolyl peptide bonds are catalyzed as well. By using the P39A vari ant of ribonuclease T1 as a substrate we find that the trans --> cis i somerization of the Tyr38-Ala39 bond in the refolding of this protein is not catalyzed by prolyl isomerases of the cyclophilin, FKBP and par vulin families. These enzymes are neither able to catalyze amide bond isomerizations in the proline-free model peptide Ala-Ala-Tyr-Ala-Ala.