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The influence of zinc(ii) on thioredoxin/glutathione disulfide exchange: QM/MM studies to explore how zinc(ii) accelerates exchange in higher dielectric environments

Arsenic(+3) and DNA methyltransferases, and arsenic speciation in tadpole and frog life stages of western clawed frogs (Silurana tropicalis) exposed to arsenate

Copper uptake by DMT1: a compensatory mechanism for CTR1 deficiency in human umbilical vein endothelial cells

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Metallomics Vol - 7 Issue - 7

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Metallomics Vol - 7 Issue - 5

Metallomics Vol - 7 Issue - 4

Metallomics Vol - 7 Issue - 3

Metallomics Vol - 7 Issue - 2

The influence of zinc(ii) on thioredoxin/glutathione disulfide exchange: QM/MM studies to explore how zinc(ii) accelerates exchange in higher dielectric environments

Content Provider	Royal Society of Chemistry (RSC)
Author	Bruce, Mitchell R. M. Kurian, Roby Bruce, Alice E. Amar, François G.
Copyright Year	2015
Abstract	QM/MM studies were performed to explore the energetics of exchange reactions of glutathione disulfide (GSSG) and the active site of thioredoxin [Cys32–Gly33–Pro34–Cys35] with and without zinc(II), in vacuum and solvated models. The activation energy for exchange, in the absence of zinc, is 29.7 kcal mol−1 for the solvated model. This is 3.3 kcal mol−1 higher than the activation energy for exchange in the gas phase, due to ground state stabilization of the active site Cys-32 thiolate in a polar environment. In the presence of zinc, the activation energy for exchange is 4.9 kcal mol−1 lower than in the absence of zinc (solvated models). The decrease in activation energy is attributed to stabilization of the charge-separated transition state, which has a 4-centered, cyclic arrangement of Zn–S–S–S with an estimated dipole moment of 4.2 D. A difference of 4.9 kcal mol−1 in activation energy would translate to an increase in rate by a factor of about 4000 for zinc-assisted thiol-disulfide exchange. The calculations are consistent with previously reported experimental results, which indicate that metal-thiolate, disulfide exchange rates increase as a function of solvent dielectric. This trend is opposite to that observed for the influence of the dielectric environment on the rate of thiol-disulfide exchange in the absence of metal. The results suggest a dynamic role for zinc in thiol-disulfide exchange reactions, involving accessible cysteine sites on proteins, which may contribute to redox regulation and mechanistic pathways during oxidative stress.
Starting Page	1265
Ending Page	1273
Page Count	9
File Format	HTM / HTML PDF
ISSN	17565901
Volume Number	7
Issue Number	8
Journal	Metallomics
DOI	10.1039/c5mt00070j
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	Oxidative stress Glutathione disulfide Cysteine Active site Redox Thioredoxin Dielectric Zinc Bioenergetics Disulfide Dipole Activation energy Solvent
Content Type	Text
Resource Type	Article
Subject	Chemistry Medicine Metals and Alloys Biochemistry Biomaterials Biophysics

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