Nonprolyl cis peptide bonds in unfolded proteins cause complex folding kinetics

被引:91
作者
Pappenberger, G
Aygün, H
Engels, JW
Reimer, U
Fischer, G
Kiefhaber, T
机构
[1] Univ Basel, Biozentrum, Biophys Chem Abt, CH-4056 Basel, Switzerland
[2] Goethe Univ Frankfurt, Inst Organ Chem, D-60439 Frankfurt, Germany
[3] Max Planck Res Unit Enzymol Prot Folding, D-06120 Halle, Germany
关键词
D O I
10.1038/87624
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 similar to0.15% 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.
引用
收藏
页码:452 / 458
页数:7
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