Abstract
Folding of tendamistat, an inhibitor of α-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.
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Pappenberger, G., Aygün, H., Engels, J. et al. Nonprolyl cis peptide bonds in unfolded proteins cause complex folding kinetics. Nat Struct Mol Biol 8, 452–458 (2001). https://doi.org/10.1038/87624
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DOI: https://doi.org/10.1038/87624
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