Nonprolyl cis peptide bonds in unfolded proteins cause complex folding kinetics

Nature Structural Biology
G PappenbergerT Kiefhaber

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.

Citations

Feb 24, 2006·Nature Structural & Molecular Biology·Catherine M EakinAndrew D Miranker
Feb 29, 2008·Proceedings of the National Academy of Sciences of the United States of America·Christian LöwJochen Balbach
Sep 5, 2008·Proceedings of the National Academy of Sciences of the United States of America·Matthias J FeigeJohannes Buchner
Nov 25, 2004·European Journal of Biochemistry·Maria D CrespoMark S Searle
Jun 25, 2008·Annual Review of Biophysics·Jayant B Udgaonkar
Nov 28, 2012·PloS One·Greta HultqvistPer Jemth
Sep 21, 2005·Proceedings of the National Academy of Sciences of the United States of America·Annett BachmannHans Peter Bächinger
Mar 4, 2003·Proceedings of the National Academy of Sciences of the United States of America·Elizabeth RhoadesGilad Haran
Feb 13, 2016·Journal of Chemical Theory and Computation·Chris NealeAngel E Garcia
Jul 27, 2004·Protein Science : a Publication of the Protein Society·Yun-Ru Chen, A Clay Clark
Oct 29, 2018·Journal of Computational Chemistry·Vladimir MironovDmitri G Fedorov
Apr 24, 2012·Journal of Peptide Science : an Official Publication of the European Peptide Society·Claudia KunzHans-Jörg Hofmann
Apr 4, 2012·Current Protocols in Protein Science·Elizabeth R Morris, Mark S Searle
Apr 10, 2002·The Journal of Biological Chemistry·Kimberly A StieglitzBoguslaw Stec
Mar 20, 2016·The Biochemical Journal·Marten VillmowCordelia Schiene-Fischer
Aug 19, 2016·Chemistry : a European Journal·Harish JangraHendrik Zipse
Oct 30, 2004·Chemistry : a European Journal·Jianzhang ZhaoCordelia Schiene-Fischer
Feb 19, 2011·Journal of Molecular Biology·Ingrid DeVriesElizabeth A Komives
Jun 12, 2008·The Journal of Physical Chemistry. B·Simon MathieuGeorges Trinquier
Feb 9, 2010·The Journal of Physical Chemistry. B·Khanh NguyenDallas L Rabenstein
Jul 10, 2003·Journal of Molecular Biology·Andrew T RussoD W Bolen
Jul 16, 2003·Journal of Molecular Biology·Stefano GianniHeinrich Roder
Jul 4, 2006·Journal of Molecular Biology·Maria D CrespoMark S Searle
Oct 12, 2019·Journal of the American Chemical Society·Trevor Harris, David M Chenoweth
Jul 8, 2014·The Journal of Physical Chemistry. a·Richard J CooperEvan R Williams
Apr 3, 2007·Journal of the American Chemical Society·Dirk WildemannGunter Fischer
Oct 20, 2006·The Journal of Physical Chemistry. B·Young Kee Kang
Apr 1, 2004·Journal of the American Chemical Society·Yves A MantzGlenn J Martyna
Oct 6, 2005·Journal of the American Chemical Society·Romuald Poteau, Georges Trinquier
Jul 10, 2003·Chemical Reviews·Christophe Dugave, Luc Demange

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