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Collet J.-F.,Catholic University of Louvain | Collet J.-F.,Brussels Center for Redox Biology | Messens J.,Brussels Center for Redox Biology | Messens J.,Vrije Universiteit Brussel
Antioxidants and Redox Signaling | Year: 2010

Thioredoxins are ubiquitous antioxidant enzymes that play important roles in many health-related cellular processes. As such, the fundamental knowledge of how these enzymes work is of prime importance for understanding cellular redox mechanisms and for laying the ground for the development of future therapeutic approaches. Over the past 40 years, a really impressive amount of data has been published on thioredoxins. Here, we review the most significant results that have contributed to our knowledge regarding the structure, the function, and the mechanism of these crucial enzymes. © 2010, Mary Ann Liebert, Inc. Source

Messens J.,Brussels Center for Redox Biology | Messens J.,Vrije Universiteit Brussel | Collet J.-F.,Brussels Center for Redox Biology | Collet J.-F.,Catholic University of Louvain
Antioxidants and Redox Signaling | Year: 2013

The major function of disulfide bonds is not only the stabilization of protein structures. Over the last 30 years, a change in perspective took place driven by groundbreaking experiments, which promoted disulfide bonds to central players in essential thiol-disulfide exchange reactions involved in signal transduction, thiol protection, and redox homeostasis regulation. This new view stimulated redox research and led to the discovery of novel redox pathways, redox enzymes, and new low-molecular-weight thiols. These redox-sensitive molecules operate along diverse pathways via a dynamic thiol-disulfide mechanism in which disulfide bonds are reversibly formed and reduced, thereby switching the molecules between different conformational and functional states. It is now clear that disulfide bonds play a pivotal role in cellular reduction and oxidation processes. However, in spite of the fundamental cell biological and medical importance of the thiol-disulfide exchange switches, we are only beginning to understand their principles of specificity, their mechanism of action, and their role in signal transduction. Our further progress in understanding the thiol-disulfide switches will strongly depend on the chemical tools and on the technological advances that will be made in the development of new methodologies. Antioxid. Redox Signal. 18, 1594-1596. © Copyright 2013, Mary Ann Liebert, Inc. 2013. © 2013 Mary Ann Liebert, Inc. Source

Roszczenko P.,University of Warsaw | Radomska K.A.,University of Warsaw | Wywial E.,International Institute of Molecular and Cell Biology | Collet J.-F.,Catholic University of Louvain | And 2 more authors.
PLoS ONE | Year: 2012

Background: The formation of a disulfide bond between two cysteine residues stabilizes protein structure. Although we now have a good understanding of the Escherichia coli disulfide formation system, the machineries at work in other bacteria, including pathogens, are poorly characterized. Thus, the objective of this work was to improve our understanding of the disulfide formation machinery of Helicobacter pylori, a leading cause of ulcers and a risk factor for stomach cancer worldwide. Methods and Results: The protein HP0231 from H. pylori, a structural counterpart of E. coli DsbG, is the focus of this research. Its function was clarified by using a combination of biochemical, microbiological and genetic approaches. In particular, we determined the biochemical properties of HP0231 as well as its redox state in H. pylori cells. Conclusion: Altogether our results show that HP0231 is an oxidoreductase that catalyzes disulfide bond formation in the periplasm. We propose to call it HpDsbA. © 2012 Roszczenko et al. Source

Olah J.,Budapest University of Technology and Economics | Van Bergen L.,Vrije Universiteit Brussel | De Proft F.,Vrije Universiteit Brussel | Roos G.,Vrije Universiteit Brussel | Roos G.,Brussels Center for Redox Biology
Journal of Biomolecular Structure and Dynamics | Year: 2015

Protein thiol/sulfenic acid oxidation potentials provide a tool to select specific oxidation agents, but are experimentally difficult to obtain. Here, insights into the thiol sulfenylation thermodynamics are obtained from model calculations on small systems and from a quantum mechanics/molecular mechanics (QM/MM) analysis on human 2-Cys peroxiredoxin thioredoxin peroxidase B (Tpx-B). To study thiol sulfenylation in Tpx-B, our recently developed computational method to determine reduction potentials relatively compared to a reference system and based on reaction energies reduction potential from electronic energies is updated. Tpx-B forms a sulfenic acid (R-SO-) on one of its active site cysteines during reactive oxygen scavenging. The observed effect of the conserved active site residues is consistent with the observed hydrogen bond interactions in the QM/MM optimized Tpx-B structures and with free energy calculations on small model systems. The ligand effect could be linked to the complexation energies of ligand L with CH3S- and CH3SO-. Compared to QM only calculations on Tpx-Bs active site, the QM/MM calculations give an improved understanding of sulfenylation thermodynamics by showing that other residues from the protein environment other than the active site residues can play an important role. © 2014 Taylor & Francis. Source

Van Laer K.,Vlaams Instituut voor Biotechnologie VIB | Van Laer K.,Vrije Universiteit Brussel | Van Laer K.,Brussels Center for Redox Biology | Hamilton C.J.,University of East Anglia | And 3 more authors.
Antioxidants and Redox Signaling | Year: 2013

Significance: Oxidative stress is widely invoked in inflammation, aging, and complex diseases. To avoid unwanted oxidations, the redox environment of cellular compartments needs to be tightly controlled. The complementary action of oxidoreductases and of high concentrations of low-molecular-weight (LMW) nonprotein thiols plays an essential role in maintaining the redox potential of the cell in balance. Recent Advances: While LMW thiols are central players in an extensive range of redox regulation/metabolism processes, not all organisms use the same thiol cofactors to this effect, as evidenced by the recent discovery of mycothiol (MSH) and bacillithiol (BSH) among different gram-positive bacteria. Critical Issues: LMW thiol-disulfide exchange processes and their cellular implications are often oversimplified, as only the biology of the free thiols and their symmetrical disulfides is considered. In bacteria under oxidative stress, especially where concentrations of different LMW thiols are comparable [e.g., BSH, coenzyme A (CoA), and cysteine (Cys) in many low-G+C gram-positive bacteria (Firmicutes)], mixed disulfides (e.g., CoASSB and CySSCoA) must surely be major thiol-redox metabolites that need to be taken into consideration. Future Directions: There are many microorganisms whose LMW thiol-redox buffers have not yet been identified (either bioinformatically or experimentally). Many elements of BSH and MSH redox biochemistry remain to be explored. The fundamental biophysical properties, thiol pKa and redox potential, have not yet been determined, and the protein interactome in which the biothiols MSH and BSH are involved needs further exploration. © 2013 Mary Ann Liebert, Inc. Source

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