Ligand exchange during cytochrome c folding

Syun-Ru Yeh, Satoshi Takahashi, Baochen Fan, Denis L. Rousseau

Research output: Contribution to journalArticle

132 Citations (Scopus)

Abstract

Submillisecond folding of cytochrome c reveals that a nascent phase appears within the mixing dead time of 100 μs, followed by a ligand exchange reaction during which His 26/33, water and Met 80 are inter-exchanged as haem ligands through a thermodynamically controlled equilibrium. In the ligand exchange phase, the rate of formation of a misfolded histidine-histidine coordinated state (HH) decreases by two orders of magnitude as the pH is reduced from 5.9 to 4.5 due to the protonation of the misligated His 26/33. The activation energy barriers for the transitions from the histidine-water coordinated form (HW) to the histidine-methionine coordinated form and the HH form are 18 and 4 kcal mol-1 respectively, at pH 4.8. The activation energy barrier for protein to escape from the misligated HH to the HW form was measured to be 12 kcal mol-1, demonstrating the kinetic trapping effect of the misligated bis-histidine form. The development of the polypeptide tertiary structure near the haem is concomitant with the coordination of the native haem axial ligand.

Original languageEnglish (US)
Pages (from-to)51-56
Number of pages6
JournalNature Structural Biology
Volume4
Issue number1
DOIs
StatePublished - Jan 1997

Fingerprint

Cytochromes c
Histidine
Ligands
Heme
Energy barriers
Activation energy
Water
Protonation
Methionine
Peptides
Kinetics
Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Structural Biology
  • Genetics

Cite this

Ligand exchange during cytochrome c folding. / Yeh, Syun-Ru; Takahashi, Satoshi; Fan, Baochen; Rousseau, Denis L.

In: Nature Structural Biology, Vol. 4, No. 1, 01.1997, p. 51-56.

Research output: Contribution to journalArticle

Yeh, Syun-Ru ; Takahashi, Satoshi ; Fan, Baochen ; Rousseau, Denis L. / Ligand exchange during cytochrome c folding. In: Nature Structural Biology. 1997 ; Vol. 4, No. 1. pp. 51-56.
@article{5a608e2a0974498a8506a633bd9bd51e,
title = "Ligand exchange during cytochrome c folding",
abstract = "Submillisecond folding of cytochrome c reveals that a nascent phase appears within the mixing dead time of 100 μs, followed by a ligand exchange reaction during which His 26/33, water and Met 80 are inter-exchanged as haem ligands through a thermodynamically controlled equilibrium. In the ligand exchange phase, the rate of formation of a misfolded histidine-histidine coordinated state (HH) decreases by two orders of magnitude as the pH is reduced from 5.9 to 4.5 due to the protonation of the misligated His 26/33. The activation energy barriers for the transitions from the histidine-water coordinated form (HW) to the histidine-methionine coordinated form and the HH form are 18 and 4 kcal mol-1 respectively, at pH 4.8. The activation energy barrier for protein to escape from the misligated HH to the HW form was measured to be 12 kcal mol-1, demonstrating the kinetic trapping effect of the misligated bis-histidine form. The development of the polypeptide tertiary structure near the haem is concomitant with the coordination of the native haem axial ligand.",
author = "Syun-Ru Yeh and Satoshi Takahashi and Baochen Fan and Rousseau, {Denis L.}",
year = "1997",
month = "1",
doi = "10.1038/nsb0197-51",
language = "English (US)",
volume = "4",
pages = "51--56",
journal = "Nature Structural and Molecular Biology",
issn = "1545-9993",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Ligand exchange during cytochrome c folding

AU - Yeh, Syun-Ru

AU - Takahashi, Satoshi

AU - Fan, Baochen

AU - Rousseau, Denis L.

PY - 1997/1

Y1 - 1997/1

N2 - Submillisecond folding of cytochrome c reveals that a nascent phase appears within the mixing dead time of 100 μs, followed by a ligand exchange reaction during which His 26/33, water and Met 80 are inter-exchanged as haem ligands through a thermodynamically controlled equilibrium. In the ligand exchange phase, the rate of formation of a misfolded histidine-histidine coordinated state (HH) decreases by two orders of magnitude as the pH is reduced from 5.9 to 4.5 due to the protonation of the misligated His 26/33. The activation energy barriers for the transitions from the histidine-water coordinated form (HW) to the histidine-methionine coordinated form and the HH form are 18 and 4 kcal mol-1 respectively, at pH 4.8. The activation energy barrier for protein to escape from the misligated HH to the HW form was measured to be 12 kcal mol-1, demonstrating the kinetic trapping effect of the misligated bis-histidine form. The development of the polypeptide tertiary structure near the haem is concomitant with the coordination of the native haem axial ligand.

AB - Submillisecond folding of cytochrome c reveals that a nascent phase appears within the mixing dead time of 100 μs, followed by a ligand exchange reaction during which His 26/33, water and Met 80 are inter-exchanged as haem ligands through a thermodynamically controlled equilibrium. In the ligand exchange phase, the rate of formation of a misfolded histidine-histidine coordinated state (HH) decreases by two orders of magnitude as the pH is reduced from 5.9 to 4.5 due to the protonation of the misligated His 26/33. The activation energy barriers for the transitions from the histidine-water coordinated form (HW) to the histidine-methionine coordinated form and the HH form are 18 and 4 kcal mol-1 respectively, at pH 4.8. The activation energy barrier for protein to escape from the misligated HH to the HW form was measured to be 12 kcal mol-1, demonstrating the kinetic trapping effect of the misligated bis-histidine form. The development of the polypeptide tertiary structure near the haem is concomitant with the coordination of the native haem axial ligand.

UR - http://www.scopus.com/inward/record.url?scp=0031027088&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031027088&partnerID=8YFLogxK

U2 - 10.1038/nsb0197-51

DO - 10.1038/nsb0197-51

M3 - Article

C2 - 8989324

AN - SCOPUS:0031027088

VL - 4

SP - 51

EP - 56

JO - Nature Structural and Molecular Biology

JF - Nature Structural and Molecular Biology

SN - 1545-9993

IS - 1

ER -