How the disulfide conformation determines the disulfide/thiol redox potential
- PMID: 24256142
- DOI: 10.1080/07391102.2013.851034
How the disulfide conformation determines the disulfide/thiol redox potential
Abstract
Protein disulfides can adopt a wide variety of conformations, each having different energies. Limited experimental data suggest that disulfides adopting a high energy have an enhanced likelihood for reduction, but the exact nature of this relation is not clear. Using a computational approach, we give insight on the conformational dependence of the redox behavior of the disulfide bond, which relates structure to reactivity. The relative energy of different conformations of the diethyl disulfide model system correlates with the disulfide/thiol redox potential E°. Insight in the calculated redox potentials is obtained via quantitative molecular orbital theory, and via the decomposition of E° into a vertical electron affinity and a subsequent reorganization term. We have identified the determinants of the disulfide conformational energies and characterized the barrier to rotation around the disulfide bond. Our findings on the diethyl disulfide model system can be transferred to examples from the Protein Data Base. In conclusion, strained disulfide conformations with a high conformational energy have a large tendency to be reduced. Upon reduction, unfavorable interactions are released. This explains why reorganization effects and not a higher tendency to accept electrons account for the high reduction potential of high-energy disulfides.
Keywords: conformation; disulfide; disulfide/thiol redox potential; quantitative MO theory; structure–reactivity relations.
Similar articles
-
High torsional energy disulfides: relationship between cross-strand disulfides and right-handed staples.J Bioinform Comput Biol. 2006 Feb;4(1):155-68. doi: 10.1142/s0219720006001734. J Bioinform Comput Biol. 2006. PMID: 16568548
-
Thiol-Disulfide Exchange Reactions in the Mammalian Extracellular Environment.Annu Rev Chem Biomol Eng. 2016 Jun 7;7:197-222. doi: 10.1146/annurev-chembioeng-080615-033553. Epub 2016 Mar 17. Annu Rev Chem Biomol Eng. 2016. PMID: 27023663 Free PMC article. Review.
-
Redox potentials of protein disulfide bonds from free-energy calculations.J Phys Chem B. 2015 Apr 30;119(17):5386-91. doi: 10.1021/acs.jpcb.5b01051. Epub 2015 Apr 21. J Phys Chem B. 2015. PMID: 25856548
-
Effects of redox buffer properties on the folding of a disulfide-containing protein: dependence upon pH, thiol pKa, and thiol concentration.J Biotechnol. 2005 Feb 9;115(3):279-90. doi: 10.1016/j.jbiotec.2004.09.005. Epub 2004 Nov 21. J Biotechnol. 2005. PMID: 15639090
-
Protein disulfides and protein disulfide oxidoreductases in hyperthermophiles.FEBS J. 2006 Sep;273(18):4170-85. doi: 10.1111/j.1742-4658.2006.05421.x. Epub 2006 Aug 23. FEBS J. 2006. PMID: 16930136 Review.
Cited by
-
Gas-Phase Reactions of Dimethyl Disulfide with Aliphatic Carbanions - A Mass Spectrometry and Computational Study.J Am Soc Mass Spectrom. 2018 Mar;29(3):588-599. doi: 10.1007/s13361-017-1858-x. Epub 2018 Jan 8. J Am Soc Mass Spectrom. 2018. PMID: 29313204 Free PMC article.
-
The dithiol mechanism of class I glutaredoxins promotes specificity for glutathione as a reducing agent.Redox Biol. 2024 Dec;78:103410. doi: 10.1016/j.redox.2024.103410. Epub 2024 Oct 24. Redox Biol. 2024. PMID: 39488995 Free PMC article.
-
Self-Resetting Bistable Redox Molecular Machines for Fullerene Recognition.Org Lett. 2022 Aug 19;24(32):5879-5883. doi: 10.1021/acs.orglett.2c01856. Epub 2022 Jul 29. Org Lett. 2022. PMID: 35905434 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources