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1.
Thiol-based redox sensing in the methyltransferase associated sensor kinase RdmS in Methanosarcina acetivorans.
Fiege, K, Frankenberg-Dinkel, N
Environmental microbiology. 2019;(5):1597-1610
Abstract
Organisms have evolved signal transduction systems to quickly adapt their lifestyle to internal and environmental changes. While protein kinases and two-component systems are widely distributed in Bacteria, they are also found in Archaea but are less diversified and abundant. In this work, we analysed the function of the kinase RdmS and its role in a putative two-component system in the methanogenic archaeon Methanosarcina acetivorans. RdmS is encoded upstream of the regulator MsrF, which activates the expression of the corrinoid/methyltransferase fusion protein MtsD. In contrast to a typical bacterial histidine kinase, RdmS lacks a membrane domain and the conserved histidine residue for phosphorylation, indicating a different mechanism of signal transduction in comparison to bacterial counterparts. RdmS covalently binds a heme cofactor and is thereby able to bind small molecules like CO and dimethyl sulfide. Interestingly, RdmS possesses a redox-dependent autophosphorylation activity, which, however, is independent of the bound heme cofactor. In fact, our experimental data suggest a thiol-based redox sensing mechanism by RdmS. Moreover, we were able to show that RdmS interacts with the regulator protein MsrF. From these data, we conclude RdmS to be a thiol-based kinase sensing redox changes and forming an archaeal multicomponent system with the regulators MsrG/F/C.
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2.
The role of thiols in antioxidant systems.
Ulrich, K, Jakob, U
Free radical biology & medicine. 2019;:14-27
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Abstract
The sulfur biochemistry of the thiol group endows cysteines with a number of highly specialized and unique features that enable them to serve a variety of different functions in the cell. Typically highly conserved in proteins, cysteines are predominantly found in functionally or structurally crucial regions, where they act as stabilizing, catalytic, metal-binding and/or redox-regulatory entities. As highly abundant low molecular weight thiols, cysteine thiols and their oxidized disulfide counterparts are carefully balanced to maintain redox homeostasis in various cellular compartments, protect organisms from oxidative and xenobiotic stressors and partake actively in redox-regulatory and signaling processes. In this review, we will discuss the role of protein thiols as scavengers of hydrogen peroxide in antioxidant enzymes, use thiol peroxidases to exemplify how protein thiols contribute to redox signaling, provide an overview over the diverse set of low molecular weight thiol-based redox systems found in biology, and illustrate how thiol-based redox systems have evolved not only to protect against but to take full advantage of a world full of molecular oxygen.
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3.
Loss and formation of malodorous volatile sulfhydryl compounds during wine storage.
Kreitman, GY, Elias, RJ, Jeffery, DW, Sacks, GL
Critical reviews in food science and nutrition. 2019;(11):1728-1752
Abstract
Volatile sulfur compounds (VSCs), particularly low molecular weight sulfhydryls like hydrogen sulfide (H2S) and methanethiol (MeSH), are often observed in wines with sulfurous off-aromas. Recent work has shown both H2S and MeSH can increase up to a few µM (> 40 µg/L) during anoxic storage, but the identity of the latent sources of these sulfhydryls is still disputed. This review critically evaluates the latent precursors and pathways likely to be responsible for the loss and formation of these sulfhydryls during wine storage based on the existing enology literature as well as studies from food chemistry, geochemistry, biochemistry, and synthetic chemistry. We propose that three precursor classes have sufficient concentration and metastability to serve as latent sulfhydryl precursors in wine: 1) transition metal-sulfhydryl complexes, particularly those formed following Cu(II) addition, which are released under anoxic conditions through an unknown mechanism; 2) asymmetric disulfides, polysulfanes, and (di)organopolysulfanes formed through transition-metal mediated oxidation (e.g., Cu(II)) of sulfhydryls or pesticide degradation, and released through sulfitolysis, metal-catalyzed thiol-disulfide exchange or related reactions; 3) S-alkylthioacetates, primarily formed during fermentation, and releasable hydrolytically. Some evidence also exists for S-amino acids serving as precursors. Based on these findings, we propose a "decision tree" approach to choosing appropriate strategies for managing wines with sulfurous off-aromas.
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4.
Coenzyme A: a protective thiol in bacterial antioxidant defence.
Gout, I
Biochemical Society transactions. 2019;(1):469-476
Abstract
Coenzyme A (CoA) is an indispensable cofactor in all living organisms. It is synthesized in an evolutionarily conserved pathway by enzymatic conjugation of cysteine, pantothenate (Vitamin B5), and ATP. This unique chemical structure allows CoA to employ its highly reactive thiol group for diverse biochemical reactions. The involvement of the CoA thiol group in the production of metabolically active CoA thioesters (e.g. acetyl CoA, malonyl CoA, and HMG CoA) and activation of carbonyl-containing compounds has been extensively studied since the discovery of this cofactor in the middle of the last century. We are, however, far behind in understanding the role of CoA as a low-molecular-weight thiol in redox regulation. This review summarizes our current knowledge of CoA function in redox regulation and thiol protection under oxidative stress in bacteria. In this context, I discuss recent findings on a novel mode of redox regulation involving covalent modification of cellular proteins by CoA, termed protein CoAlation.
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Rapid free thiol rebound is a physiological response following cold-induced vasoconstriction in healthy humans, primary Raynaud and systemic sclerosis.
Abdulle, AE, van Roon, AM, Smit, AJ, Pasch, A, van Meurs, M, Bootsma, H, Bakker, SJL, Said, MY, Fernandez, BO, Feelisch, M, et al
Physiological reports. 2019;(6):e14017
Abstract
Raynaud's phenomenon (RP) is often the first sign of systemic sclerosis (SSc). Molecular mechanisms involved are incompletely understood, but reactive oxygen, nitrogen, and sulfur species are thought to play an important role in the pathogenesis of SSc. Free thiol groups play a protective role against oxidative stress and may represent an attractive therapeutic target. We aimed to investigate the effects of hypothermia-induced vasoconstriction on the responsiveness of redox-related markers. Thirty participants (n = 10/group [SSc, primary Raynaud's phenomenon (PRP), healthy controls (HC)]) were included in this study. Fingertip photoelectric plethysmography was performed during a standardized cooling and recovery experiment. Venous blood was collected at four predetermined time points. Free thiols, NO-derived species (nitros(yl)ated species, nitrite, nitrate), sulfate and endothelin-1 were measured. Lower baseline concentrations of free thiols were observed in PRP and SSc patients (HC: 5.87 [5.41-5.99] μmol/g; PRP: 5.17 [4.74-5.61]; SSc 5.28 [4.75-5.80], P = 0.04). Redox-related markers remained unchanged during cooling. However, an unexpected increase in systemic free thiol concentrations was observed in all groups during the recovery phase. The response of this marker differed between groups, with a higher increase found in SSc patients (HC Δ = 1.30 [1.48-1.17]; PRP Δ = 1.04 [1.06-1.03]; SSc Δ = 1.72 [1.13-1.49], P = 0.04). NO-derived species, sulfate and endothelin-1 levels remained unchanged throughout the recovery phase. This exploratory study sheds light on the rapid responsiveness of systemic free thiol concentrations following reperfusion, which may reflect overall redox balance. The robust response to reperfusion in SSc patients suggests that reductive systems involved in this response are functionally intact in these patients.
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6.
The C7-aminomethylpyrrolidine group rescues the activity of a thio-fluoroquinolone.
Lentz, SRC, Chheda, PR, Oppegard, LM, Towle, TR, Kerns, RJ, Hiasa, H
Biochimie. 2019;:24-27
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Abstract
A Mg2+-water bridge between the C-3, C-4 diketo moiety of fluoroquinolones and the conserved amino acid residues in the GyrA/ParC subunit is critical for the binding of a fluoroquinolone to a topoisomerase-DNA covalent complex. The fluoroquinolone UING-5-249 (249) can bind to the GyrB subunit through its C7-aminomethylpyrrolidine group. This interaction is responsible for enhanced activities of 249 against the wild type and quinolone-resistant mutant topoisomerases. To further evaluate the effects of the 249-GyrB interaction on fluoroquinolone activity, we examined the activities of decarboxy- and thio-249 against DNA gyrase and conducted docking studies using the structure of a gyrase-ciprofloxacin-DNA ternary complex. We found that the 249-GyrB interaction rescued the activity of thio-249 but not that of decarboxy-249. A C7-group that binds more strongly to the GyrB subunit may allow for modifications at the C-4 position, leading to a novel compound that is active against the wild type and quinolone-resistant pathogens.
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Effects of the anesthesia technique used during cesarean section on maternal-neonatal thiol disulfide homeostasis.
Akin, F, Kozanhan, B, Deniz, CD, Sahin, O, Goktepe, H, Neselioglu, S, Erel, O
Minerva anestesiologica. 2019;(11):1175-1183
Abstract
BACKGROUND Thiols are organic compounds consisting of a sulfhydryl group which exerts antioxidant effects via dynamic thiol-disulfide homeostasis (TDH). The shift towards the disulfide states signals an oxidative situation. Maternal-neonatal oxidative stress can be affected by the anesthetic technique used during cesarean section. This study aimed to evaluate the relationship between the type of anesthesia used and the maternal-neonatal TDH. METHODS ASA I-II, term parturients undergoing elective cesarean section either under general (Group G) or spinal (Group S) anesthesia were included. Blood specimens were collected preoperatively and postoperatively from the mothers and from the umbilical venous cords at delivery. TDH was studied by a new method developed by the authors (O.E. and S.N.). RESULTS Postoperative mother's native thiol, total thiol, disulfide/total thiol, native thiol/ disulfide and disulfide levels were higher in Group G than in Group S. There was no significant difference between the groups in umbilical venous cord albumin, native thiol/total thiol, disulfide, native thiol/ disulfide and total thiol/ disulfide. However, in Group G, umbilical venous cord native thiol and total thiol levels were statistically significantly lower than those in Group S. CONCLUSIONS Our results showed that general anesthesia in cesarean section leads to an impairment in TDH when compared with spinal anesthesia. Oxidative stress might be modified by the preferred anesthetic technique.
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Quantitative/qualitative analysis of adhesive-dentin interface in the presence of 10-methacryloyloxydecyl dihydrogen phosphate.
Zhou, J, Wurihan, , Shibata, Y, Tanaka, R, Zhang, Z, Zheng, K, Li, Q, Ikeda, S, Gao, P, Miyazaki, T
Journal of the mechanical behavior of biomedical materials. 2019;:71-78
Abstract
Dental adhesive provides effective retention of filling materials via adhesive-dentin hybridization. The use of co-monomers, such as 10-methacryloyloxydecyl dihydrogen phosphate (10-MDP), is thought to be crucial for hybridization owing to their ionic-binding to calcium and co-polymerization in the polymerizable adhesives. Optimal hybridization partly depends on the mechanical properties of polymerized adhesives, which are likely to be proportional to the degree of conversion ratio. This study assessed the correlation between polymerization quality and mechanical properties at the adhesive-dentin interfaces in the presence or absence of 10-MDP. In situ Raman microspectroscopy and nanoindentation tests were used concurrently to quantify the degree of conversion ratio and dynamic mechanical properties across the adhesive-dentin interfaces. Despite the excellent diffusion and apparent higher degree of co-polymerization, 10-MDP reduced the elastic modulus of the interface. The higher viscoelastic properties of the adhesive are suggestive of poor polymerization, namely polymerization linearity related to the long carboxyl chain of 10-MDP. Such reduced mechanical integrity of hybridization could also be associated with the inhibition of nano-layering between 10-MDP and mineralized tissue in the presence of hydroxyethyl methacrylate (HEMA). This potential drawback of HEMA necessitates further qualitative/quantitative characterization of adhesive-dentin hybridization using a HEMA-free/low concentration experimental 10-MDP monomer, which theoretically possesses superior chemical bonding potential to the current HEMA-rich protocol.
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Equations to Support Redox Experimentation.
Hancock, JT, Whiteman, M
Methods in molecular biology (Clifton, N.J.). 2019;:183-195
Abstract
Working with redox compounds needs to take into account the oxidation and reduction state of the compound under study. This redox state can be influenced by the media in which the compound is found, but will also be influenced by local environments. For example, this may be dictated perhaps by the locality of amino acids in the three dimensional structure of a protein. Therefore, historically, equations have been developed to enable either the redox poise of the environment to be determined, or the redox state of the compound of interest. If a compound is found in the wrong redox state-perhaps inactive-in a cell this has significant ramifications for its role, for example in cell signaling. Here, the use of such equations is discussed, with examples of the relevance to modern redox biology.
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Thiol redox-regulation for efficient adjustment of sulfur metabolism in acclimation to abiotic stress.
Telman, W, Dietz, KJ
Journal of experimental botany. 2019;(16):4223-4236
Abstract
Sulfur assimilation and sulfur metabolism are tightly controlled at the transcriptional, post-transcriptional, and post-translational levels in order to meet the demand for reduced sulfur in growth and metabolism. These regulatory mechanisms coordinate the cellular sulfhydryl supply with carbon and nitrogen assimilation in particular. Redox homeostasis is an important cellular parameter intimately connected to sulfur by means of multiple thiol modifications. Post-translational thiol modifications such as disulfide formation, sulfenylation, S-nitrosylation, persulfidation, and S-glutathionylation allow for versatile switching and adjustment of protein functions. This review focuses on redox-regulation of enzymes involved in the sulfur assimilation pathway, namely adenosine 5´-phosphosulfate reductase (APR), adenosine 5´-phosphosulfate kinase (APSK), and γ-glutamylcysteine ligase (GCL). The activity of these enzymes is adjusted at the transcriptional and post-translational level depending on physiological requirements and the state of the redox and reactive oxygen species network, which are tightly linked to abiotic stress conditions. Hormone-dependent fine-tuning contributes to regulation of sulfur assimilation. Thus, the link between oxylipin signalling and sulfur assimilation has been substantiated by identification of the so-called COPS module in the chloroplast with its components cyclophilin 20-3, O-acetylserine thiol lyase, 2-cysteine peroxiredoxin, and serine acetyl transferase. We now have a detailed understanding of how regulation enables the fine-tuning of sulfur assimilation under both normal and abiotic stress conditions.