Prolyl cis-trans isomerization as a molecular timer

Nat Chem Biol. 2007 Oct;3(10):619-29. doi: 10.1038/nchembio.2007.35.


Proline is unique in the realm of amino acids in its ability to adopt completely distinct cis and trans conformations, which allows it to act as a backbone switch that is controlled by prolyl cis-trans isomerization. This intrinsically slow interconversion can be catalyzed by the evolutionarily conserved group of peptidyl prolyl cis-trans isomerase enzymes. These enzymes include cyclophilins and FK506-binding proteins, which are well known for their isomerization-independent role as cellular targets for immunosuppressive drugs. The significance of enzyme-catalyzed prolyl cis-trans isomerization as an important regulatory mechanism in human physiology and pathology was not recognized until the discovery of the phosphorylation-specific prolyl isomerase Pin1. Recent studies indicate that both phosphorylation-dependent and phosphorylation-independent prolyl cis-trans isomerization can act as a novel molecular timer to help control the amplitude and duration of a cellular process, and prolyl cis-trans isomerization might be a new target for therapeutic interventions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Catalysis
  • Cyclophilins / chemistry
  • Cyclophilins / metabolism
  • Humans
  • Immunosuppressive Agents / pharmacology*
  • Isomerism
  • Peptides / chemistry
  • Peptides / metabolism
  • Peptidylprolyl Isomerase / chemistry
  • Peptidylprolyl Isomerase / metabolism*
  • Phosphorylation
  • Proline / chemistry
  • Proline / metabolism
  • Protein Binding
  • Protein Conformation
  • Protein Folding
  • Substrate Specificity
  • Tacrolimus Binding Proteins / chemistry
  • Tacrolimus Binding Proteins / metabolism
  • Time Factors


  • Immunosuppressive Agents
  • Peptides
  • Proline
  • Cyclophilins
  • Tacrolimus Binding Proteins
  • Peptidylprolyl Isomerase