Pseudo-prolines: induction of cis/trans-conformational interconversion by decreased transition state barriers.
Molecular events such as cis/trans isomerization of Xaa-Pro tertiary amide bonds in peptides and proteins are slow on the overall time scale of the formation of a final biostructure and are, therefore, rate limiting. In order to pursue a better understanding of the molecular events underlying such slow interconversions, we applied the recently introduced pseudo-proline (PsiPro) concept as a tool to study the dynamics of Xaa-Pro bonds by determining the kinetics and thermodynamics of cis/trans isomerism. We show that enhanced isomerization rates of tertiary amide bonds prior to a PsiPro unit in short model peptides is due to lowered transition state barriers. In addition, pronounced effects upon the dynamics of the reversible transition between helix I and II of oligoprolines containing one or several PsiPro units were observed.
Mutter
M
M
Institute of Organic Chemistry, University of Lausanne, BCH-Dorigny, CH-1015 Lausanne, Switzerland.
Wöhr
T
T
Gioria
S
S
Keller
M
M
D002918:Chymotrypsin / Q000737:chemistry; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D007536:Isomerism; D007700:Kinetics; D008968:Molecular Conformation; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry; D011392:Proline / Q000031:analogs & derivatives* / Q000737:chemistry; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry; D013816:Thermodynamics
D010455:Peptides; D011506:Proteins; D011392:Proline; D002918:Chymotrypsin