title: Prolyl cis-trans isomerization as a molecular timer.
abstract: 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.
authors: Cancer Biology Program, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 77 Avenue Louis Pasteur, NRB 1030, Boston, Massachusetts 02215, USA. klu@bidmc.harvard.edu
authors: Kun Ping
authors: KP
authors: Lu
authors: Greg
authors: G
authors: Finn
authors: Tae Ho
authors: TH
authors: Lee
authors: Linda K
authors: LK
authors: Nicholson
mesh_terms: D002384:Catalysis; D021983:Cyclophilins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007536:Isomerism; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D019696:Peptidylprolyl Isomerase / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D011392:Proline / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D013379:Substrate Specificity; D022021:Tacrolimus Binding Proteins / Q000737:chemistry / Q000378:metabolism; D013997:Time Factors
chemical_list: D007166:Immunosuppressive Agents; D010455:Peptides; D011392:Proline; D021983:Cyclophilins; D022021:Tacrolimus Binding Proteins; D019696:Peptidylprolyl Isomerase