title: Nonprolyl cis peptide bonds in unfolded proteins cause complex folding kinetics.
abstract: Folding of tendamistat, an inhibitor of alpha-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 approximately 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.
authors.affiliation: Biozentrum der Universität Basel, Abteilung Biophysikalische Chemie, Klingelbergstrasse 70, CH-4056 Basel, Switzerland.
authors.forename: G
authors.initials: G
authors.lastname: Pappenberger
authors.forename: H
authors.initials: H
authors.lastname: Aygün
authors.forename: J W
authors.initials: JW
authors.lastname: Engels
authors.forename: U
authors.initials: U
authors.lastname: Reimer
authors.forename: G
authors.initials: G
authors.lastname: Fischer
authors.forename: T
authors.initials: T
authors.lastname: Kiefhaber
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D007536:Isomerism; D007700:Kinetics; D018021:Lithium Chloride / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011392:Proline / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011487:Protein Conformation / Q000187:drug effects; D011489:Protein Denaturation; D017510:Protein Folding; D020673:Protein Renaturation / Q000187:drug effects; D013696:Temperature; D013816:Thermodynamics; D000516:alpha-Amylases / Q000037:antagonists & inhibitors
chemical_list: D001426:Bacterial Proteins; D010455:Peptides; D011392:Proline; D000516:alpha-Amylases; D018021:Lithium Chloride; C030526:tendamistate