Prolyl cis-trans isomerization as a molecular timer
KP Lu, G Finn, TH Lee, LK Nicholson - Nature chemical biology, 2007 - nature.com
KP Lu, G Finn, TH Lee, LK Nicholson
Nature chemical biology, 2007•nature.comProline 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 …
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 …
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.
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