Nature Structural Biology
8, 452 - 458 (2001)
doi:10.1038/87624
Nonprolyl cis peptide bonds in unfolded proteins cause complex folding kineticsGünter Pappenberger1, 4, Hüseyin Aygün2, Joachim W. Engels2, Ulf Reimer2, 3, Gunter Fischer3
& Thomas Kiefhaber11
Biozentrum der Universität Basel, Abteilung Biophysikalische Chemie, Klingelbergstrasse 70, CH-4056 Basel, Switzerland. 2
Institut für Organische Chemie der Universität Frankfurt, Marie Curie Strasse 11, D-60439 Frankfurt/Main, Germany. 3
Max Planck Research Unit "Enzymology of Protein Folding", Weinbergweg 22, D-06120 Halle (Saale), Germany. 4
Present address: The Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London, SW3 6JB, UK.
Correspondence should be addressed to Thomas Kiefhaber t.kiefhaber@unibas.chFolding of tendamistat, an inhibitor of  -amylase, is a fast two-state process accompanied by two minor slow reactions, which were assigned to prolyl isomerization. In a proline-free variant, 5% of the molecules still fold slowly with a rate constant of 2.5 s-1. This reaction is caused by a slow equilibrium between two populations of unfolded molecules. The time constant for this equilibration process, its sensitivity to LiCl and its temperature dependence identify it as a cis-trans isomerization of nonprolyl peptide bonds. Although nonprolyl peptide bonds have the cis conformation populating only  0.15% in unfolded proteins, their large number generates a significant fraction of slow-folding molecules. This emphasizes that heterogeneous populations in an unfolded protein can induce complex folding kinetics on various time scales.
|
