Prolyl cis-trans isomerization as a molecular timer.
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.
Lu
Kun Ping
KP
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
Finn
Greg
G
Lee
Tae Ho
TH
Nicholson
Linda K
LK
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
D007166:Immunosuppressive Agents; D010455:Peptides; D011392:Proline; D021983:Cyclophilins; D022021:Tacrolimus Binding Proteins; D019696:Peptidylprolyl Isomerase