THE MODE OF ACTION OF PEPTIDYL-PROLYL CIS TRANS ISOMERASES IN-VIVO - BINDING VS. CATALYSIS/

Polypeptides often display proline-mediated conformational substates t hat are prone to isomer-specific recognition and function. Both possib ilities can be of biological significance. Distinct families of peptid yl prolyl cis/trans isomerases (PPIases) evolved proved to be highly s pecific for proline moieties arranged in a special contest of subsites , Structural and chemical features of molecules specifically bound to the active site of PPIases served to improve catalysis of prolyl isome rization rather than ground state binding. For example, results inferr ed from receptor Ser/Thr or Tyr phosphorylation in the presence of sit e-directed FKBP12 mutant proteins provided evidence for the crucial ro le of the enzymatic activity in downregulating function of FKBP12. (C) 1998 Federation of European Biochemical Societies.