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Structural Changes in the Transition State of Protein Folding: Alternative Interpretations of Curved Chevron Plots

Otzen, Daniel E; Kristensen, Ole; Proctor, Mark and Oliveberg, Mikael LU (1999) In Biochemistry 38(20). p.6499-6511
Abstract
The interpretation of folding rates is often rationalized within the context of transition state theory. This means that the reaction rate is linked to an activation barrier, the height of which is determined by the free energy difference between a ground state (the starting point) and an apparent transition state. Changes in the folding kinetics are thus caused by effects on either the ground state, the transition state, or both. However, structural changes of the transition state are rarely discussed in connection with experimental data, and kinetic anomalies are commonly ascribed to ground state effects alone, e.g., depletion or accumulation of structural intermediates upon addition of denaturant. In this study, we present kinetic data... (More)
The interpretation of folding rates is often rationalized within the context of transition state theory. This means that the reaction rate is linked to an activation barrier, the height of which is determined by the free energy difference between a ground state (the starting point) and an apparent transition state. Changes in the folding kinetics are thus caused by effects on either the ground state, the transition state, or both. However, structural changes of the transition state are rarely discussed in connection with experimental data, and kinetic anomalies are commonly ascribed to ground state effects alone, e.g., depletion or accumulation of structural intermediates upon addition of denaturant. In this study, we present kinetic data which are best described by transition state changes. We also show that ground state effects and transition state effects are in general difficult to distinguish kinetically. The analysis is based on the structurally homologous proteins U1A and S6. Both proteins display two-state behavior, but there is a marked difference in their kinetics. S6 exhibits a classical V-shaped chevron plot (log observed rate constant vs denaturant concentration), whereas U1A's chevron plot is symmetrically curved, like an inverted bell curve. However, S6 is readily mutated to display U1A-like kinetics. The seemingly drastic effects of these mutations are readily ascribed to transition state movements where large kinetic differences result from relatively small alterations of a common free energy profile and broad activation barriers. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Biochemistry
volume
38
issue
20
pages
6499 - 6511
publisher
The American Chemical Society
external identifiers
  • scopus:0033580679
ISSN
0006-2960
DOI
10.1021/bi982819j
language
English
LU publication?
yes
id
28844316-e4a4-4372-a336-219e7e463b6a (old id 125371)
date added to LUP
2007-07-09 09:01:41
date last changed
2017-04-30 08:27:01
@article{28844316-e4a4-4372-a336-219e7e463b6a,
  abstract     = {The interpretation of folding rates is often rationalized within the context of transition state theory. This means that the reaction rate is linked to an activation barrier, the height of which is determined by the free energy difference between a ground state (the starting point) and an apparent transition state. Changes in the folding kinetics are thus caused by effects on either the ground state, the transition state, or both. However, structural changes of the transition state are rarely discussed in connection with experimental data, and kinetic anomalies are commonly ascribed to ground state effects alone, e.g., depletion or accumulation of structural intermediates upon addition of denaturant. In this study, we present kinetic data which are best described by transition state changes. We also show that ground state effects and transition state effects are in general difficult to distinguish kinetically. The analysis is based on the structurally homologous proteins U1A and S6. Both proteins display two-state behavior, but there is a marked difference in their kinetics. S6 exhibits a classical V-shaped chevron plot (log observed rate constant vs denaturant concentration), whereas U1A's chevron plot is symmetrically curved, like an inverted bell curve. However, S6 is readily mutated to display U1A-like kinetics. The seemingly drastic effects of these mutations are readily ascribed to transition state movements where large kinetic differences result from relatively small alterations of a common free energy profile and broad activation barriers.},
  author       = {Otzen, Daniel E and Kristensen, Ole and Proctor, Mark and Oliveberg, Mikael},
  issn         = {0006-2960},
  language     = {eng},
  number       = {20},
  pages        = {6499--6511},
  publisher    = {The American Chemical Society},
  series       = {Biochemistry},
  title        = {Structural Changes in the Transition State of Protein Folding: Alternative Interpretations of Curved Chevron Plots},
  url          = {http://dx.doi.org/10.1021/bi982819j},
  volume       = {38},
  year         = {1999},
}