Redox Biochemistry and Chemistry最新文献

{"title":"Decoding the enigmatic last gasotransmitter. The intriguing journey of HNO: From hidden origins to clues on reactivity and detection","authors":"Sebastian A. Suarez","doi":"10.1016/j.rbc.2024.100024","DOIUrl":"10.1016/j.rbc.2024.100024","url":null,"abstract":"<div><p>This review focuses on HNO, a molecule of immense chemical and biological importance that has intrigued scientists for decades. Despite its elusive and transient nature, HNO may play an important role in various physiological processes, particularly in cardiovascular regulation. This review thoroughly examines the formation, chemical properties, and biological significance of HNO and highlights ongoing research efforts to unravel its mysteries. Challenges in studying HNO arise from its high reactivity, short half-life, and complex interactions with other nitrogen oxides, particularly nitric oxide. Detection and quantification of HNO in biological systems pose difficulties, prompting the development of advanced techniques. Active research into endogenous HNO formation is revealing intricate pathways within biological systems, the elucidation of which is crucial for exploiting its therapeutic potential. The multifaceted role of HNO in cardiovascular regulation, influencing vasorelaxation, blood pressure reduction, and enhanced cardiac contractility, underscores its profound impact on the circulatory system. Ongoing research holds promise for treating conditions such as hypertension and heart failure. As clinical applications expand, HNO research may unlock treatments for cardiovascular disease, inflammatory disorders, and cancer. The recent discovery of endogenous HNO production in plants adds a new dimension. While numerous clues have emerged, the scientific saga underscores that mysteries persist, evolve, and beckon to perpetual exploration in the realm of science.</p></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"8 ","pages":"Article 100024"},"PeriodicalIF":0.0,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773176624000051/pdfft?md5=072377c74312656eca6afa81588537c0&pid=1-s2.0-S2773176624000051-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140763633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxidized guanosines induce mitochondrial dysfunction and loss of viability in β-cells","authors":"Inga Sileikaite-Morvaközi ,&nbsp;Ksenia Morozova ,&nbsp;Nadezda A. Brazhe ,&nbsp;Olga Sosnovtseva ,&nbsp;Claus Desler ,&nbsp;Thomas Mandrup-Poulsen ,&nbsp;Michael J. Davies ,&nbsp;Clare L. Hawkins","doi":"10.1016/j.rbc.2024.100022","DOIUrl":"https://doi.org/10.1016/j.rbc.2024.100022","url":null,"abstract":"<div><p>The production of reactive oxygen species and oxidative stress promote β-cell dysfunction and impair insulin secretion, thereby contributing to the pathogenesis of type 2 diabetes mellitus (T2DM). The nucleobase guanine is highly sensitive to oxidation, which results in the formation of 8-oxoguanosine (8oxoG) and 8-oxodeoxyguanosine (8oxodG). The urinary excretion of 8oxoG is associated with the risk of mortality in people with T2DM, including from diabetic complications such as cardiovascular disease. However, the cellular mechanisms responsible for this association are poorly defined. Therefore, in this study, we examined the effect of 8oxoG, 8oxodG and other oxidized guanosine derivatives, on the INS-1E β-cell line. Exposure of INS-1E cells to 8oxoG and 8oxodG decreased metabolic activity and promoted cell death by apoptosis. The change in cell viability was similar to that induced by treatment of INS-1E cells with the inflammatory cytokines interleukin 1β (Il-1β) and tumour necrosis factor α (TNFα). Changes in mitochondrial membrane permeability and superoxide radical formation were also observed with 8oxoG, but there was no significant change in the oxidation state of mitochondrial cytochromes or hydrogen peroxide levels in the INS-1E cells. Interestingly, exposure to 8oxoG and 8-oxodG also increased the mRNA expression of stress response genes, including NADPH dehydrogenase quinone 1 (NQO1), and thioredoxin-interacting protein (TXNIP). Together, these results support a potential role of oxidized guanosine derivatives in the induction of β-cell dysfunction, which could be relevant to the pathogenesis of T2DM.</p></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"8 ","pages":"Article 100022"},"PeriodicalIF":0.0,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773176624000038/pdfft?md5=bdee5885ca4a34f13fa105f9aac9f767&pid=1-s2.0-S2773176624000038-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140539119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lactoperoxidase catalytically oxidize hydrogen sulfide via intermediate formation of sulfheme derivatives","authors":"Bessie B. Ríos-González ,&nbsp;Andrea Domán ,&nbsp;Tamás Ditrói ,&nbsp;Dorottya Garai ,&nbsp;Leishka D. Crespo ,&nbsp;Gary J. Gerfen ,&nbsp;Paul G. Furtmüller ,&nbsp;Péter Nagy ,&nbsp;Juan López-Garriga","doi":"10.1016/j.rbc.2024.100021","DOIUrl":"https://doi.org/10.1016/j.rbc.2024.100021","url":null,"abstract":"<div><p>The biological chemistry of hydrogen sulfide (H₂S) with physiologically important heme proteins is in the focus of redox biology research. In this study, we investigated the interactions of lactoperoxidase (LPO) with H₂S in the presence and absence of molecular dioxygen (O₂) or hydrogen peroxide (H₂O₂). Under anaerobic conditions, native LPO forms no heme-H₂S complex upon sulfide exposure. However, under aerobic conditions or in the presence of H₂O₂ the formation of both ferrous and ferric sulfheme (sulfLPO) derivatives was observed based on the appearances of their characteristic optical absorptions at 638 nm and 727 nm, respectively. Interestingly, we demonstrate that LPO can catalytically oxidize H₂S by H₂O₂ via intermediate formation of relatively short-lived ferrous and ferric sulfLPO derivatives. Pilot product analyses suggested that the turnover process generates oxidized sulfide species, which include sulfate (SO₄²⁻) and inorganic polysulfides (HS_x⁻; x = 2–5). These results indicated that H₂S can serve as a non-classical LPO substrate by inducing a reversible sulfheme-like modification of the heme porphyrin ring during turnover. Furthermore, electron paramagnetic resonance data suggest that H₂S can act as a scavenger of H₂O₂ in the presence of LPO without detectable formation of any carbon-centered protein radical species, suggesting that H₂S might be capable of protecting the enzyme from radical-mediated damage. We propose possible mechanisms, which explain our results as well as contrasting observations with other heme proteins, where either no sulfheme formation was observed or the generation of sulfheme derivatives provided a dead end for enzyme functions.</p></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"8 ","pages":"Article 100021"},"PeriodicalIF":0.0,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773176624000026/pdfft?md5=c98d3efbf75f1105ec44b5dd1c758983&pid=1-s2.0-S2773176624000026-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140549042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemistry of nitrogen dioxide and its biological implicatios","authors":"Sara Goldstein ,&nbsp;Amram Samuni","doi":"10.1016/j.rbc.2024.100020","DOIUrl":"10.1016/j.rbc.2024.100020","url":null,"abstract":"<div><p>Nitrogen dioxide (^•NO₂) is a radical gas that forms part of air pollution and is produced chemically, photochemically and by ionizing radiation in aqueous and non-aqueous solutions as well as by various endogenous pathways in biological systems. This review describes the: (<em>i</em>) sources of ^•NO₂; (<em>ii</em>) kinetics and mechanism of ^•NO₂ reactions; (<em>iii</em>) ^•NO₂ as a key player in cellular oxidative and nitrosative stress leading to pathological conditions, and <em>(iv)</em> use of diverse antioxidants to reduce ^•NO₂ toxic effects.</p></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"7 ","pages":"Article 100020"},"PeriodicalIF":0.0,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773176624000014/pdfft?md5=1281d8224d83c88cf2e2284ffe34567c&pid=1-s2.0-S2773176624000014-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140268890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation of cellular signalling pathways and apoptosis by the aldehyde acrolein – A major environmental hazard","authors":"Diana A. Averill-Bates,&nbsp;André Tanel","doi":"10.1016/j.rbc.2023.100019","DOIUrl":"10.1016/j.rbc.2023.100019","url":null,"abstract":"<div><p>Interest in the molecular actions of acrolein has increased in light of growing knowledge that implicates this reactive aldehyde in a wide range of pathophysiologies including neurodegenerative diseases, various lung disorders including chronic obstructive pulmonary disease, atherosclerosis, and certain cancers. This is rendered complex because acrolein exists in mixtures of environmental pollutants. Reactive α,β-unsaturated aldehydes like acrolein are major components of common environmental pollutants like cigarettes, automobile exhaust, and smoke from wood, coal, forest and house fires. It is a natural constituent of several foods and is generated in the human body during inflammation or oxidation of unsaturated lipids. Acrolein is also a toxic metabolic product of the widely used anticancer drug cyclophosphamide and is generated from the enzymatic oxidation of polyamines. It is a toxic by-product of lipid peroxidation and has been implicated as a mediator of oxidative damage in cells and tissues. The purpose of this review is to assess the literature about the activation of cell signalling pathways and transcription factors, and cell survival and cell death pathways by acrolein. Several reports show that anti-apoptosis processes dominate at lower dose exposures to acrolein, whereas pro-apoptotic processes and necrosis dominate at higher dose exposures. There has been improved understanding about the deleterious molecular and cellular mechanisms that are triggered in cells in response to acrolein injury. However, more progress is required to define the contributions of acrolein to human diseases and to design efficient therapeutic strategies based on the biochemical modulation of acrolein activity.</p></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"7 ","pages":"Article 100019"},"PeriodicalIF":0.0,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773176623000184/pdfft?md5=9c33fed1db3a45958274b57c9b23009a&pid=1-s2.0-S2773176623000184-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138988898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selenocyanate (SeCN−) acts as an efficient competitive substrate for myeloperoxidase and decreases biological damage induced by hypochlorous acid","authors":"Xing Zhang ,&nbsp;Shuqi Xu ,&nbsp;Christine Y. Chuang ,&nbsp;Brian J. Day ,&nbsp;Clare L. Hawkins ,&nbsp;Michael J. Davies","doi":"10.1016/j.rbc.2023.100018","DOIUrl":"https://doi.org/10.1016/j.rbc.2023.100018","url":null,"abstract":"<div><p>The leukocyte-derived enzyme myeloperoxidase (MPO) is a key component of the innate immune response and mediates the killing of pathogens via the generation of the powerful oxidant hypochlorous acid (HOCl). Unintended or excessive formation of this species can however result in damage to host tissues, and this is linked with multiple pathologies associated with acute or chronic inflammation. The active (Compound I) form of MPO is promiscuous and can oxidize multiple alternative anions, in addition to the Cl⁻ used to generate HOCl. These alternative substrates may therefore modulate MPO-mediated HOCl damage. In the current study we examined the hypothesis that selenocyanate (SeCN⁻), the selenium analogue of thiocyanate (SCN⁻, a well-established competitive MPO substrate) would inhibit HOCl-mediated damage to human plasma fibronectin (hpFN) or the extracellular matrix laid down by human coronary artery smooth muscle cells. SeCN⁻ modulated HOCl and MPO-mediated damage, in a dose-dependent manner. These data are consistent with SeCN⁻ acting as both a competitive substrate for Compound I of MPO (with IC₅₀ ∼23 μM), and as a direct scavenger of HOCl. Inhibition of protein damage by SeCN⁻ was also detected in the presence of the physiological anions Br⁻, I⁻ and SCN⁻ at the concentrations typically present in human plasma, consistent with a high affinity of SeCN⁻ for MPO Compound I. In addition, the protective effects of SeCN⁻ and SCN⁻, as competitive MPO substrates, were additive. Together these data indicate that modest concentrations of SeCN⁻ can, like its sulfur analogue SCN⁻, act as an effective modulator of inflammation-induced damage.</p></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"7 ","pages":"Article 100018"},"PeriodicalIF":0.0,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773176623000172/pdfft?md5=4ce4a3466ab4e55a3ca75be7e8b6ea2f&pid=1-s2.0-S2773176623000172-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138549547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Arsenic exposure and increased C-reactive protein are independently associated with lower erythrocyte glutathione peroxidase activity in Bangladeshi children","authors":"Dorian M. Cheff ,&nbsp;Helena Skröder ,&nbsp;Evana Akhtar ,&nbsp;Qing Cheng ,&nbsp;Matthew D. Hall ,&nbsp;Rubhana Raqib ,&nbsp;Maria Kippler ,&nbsp;Marie Vahter ,&nbsp;Elias S.J. Arnér","doi":"10.1016/j.rbc.2023.100015","DOIUrl":"https://doi.org/10.1016/j.rbc.2023.100015","url":null,"abstract":"<div><p>Toxic metal contaminants present in food and water have widespread effects on health and disease. Chalcophiles, such as arsenic, cadmium, and mercury, show a high affinity to selenium and exposure to these metals could have a modulating effect on enzymes dependent on selenocysteine in their active sites. The aim of this study was to assess the influence of these metals on the activity of the selenoprotein glutathione peroxidase 1 (GPX1) in erythrocytes of 100 children residing in rural Bangladesh, where drinking water often contains arsenic. GPX1 expression, as measured using high-throughput immunoblotting, showed little correlation with GPX activity (<em>r</em>_<em>s</em> = 0.02, p = 0.87) in blood samples. Toxic metals and selenium measured in erythrocytes using inductively coupled plasma mass spectrometry (ICP-MS) and <em>C</em>-reactive protein (CRP) measured in plasma, were all considered as effectors of this divergence in GPX enzymatic activity. Arsenic concentrations in erythrocytes were most influential for GPX1 activity (<em>r</em>_<em>s</em> = −0.395, p &lt; 0.0001), and CRP levels also negatively impacted GPX1 activity (<em>r</em>_<em>s</em> = −0.443, p &lt; 0.0001). These effects appear independent of each other as arsenic concentrations and CRP showed no correlation (<em>r</em>_<em>s</em> = 0.124, p = 0.2204). Erythrocyte selenium, cadmium, and mercury did not show any correlation with GPX1 activity, nor with CRP or arsenic. Our findings suggest that childhood exposure to inorganic arsenic, as well as inflammation triggering the release of CRP, may negatively affect GPX1 activity in erythrocytes.</p></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"5 ","pages":"Article 100015"},"PeriodicalIF":0.0,"publicationDate":"2023-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49726672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reactivity of mitochondrial peroxiredoxins with biological hydroperoxides","authors":"Madia Trujillo ,&nbsp;Lucía Piacenza ,&nbsp;Rafael Radi","doi":"10.1016/j.rbc.2023.100017","DOIUrl":"https://doi.org/10.1016/j.rbc.2023.100017","url":null,"abstract":"<div><p>Mitochondria are main sources of biological hydroperoxides, including hydrogen peroxide, peroxynitrite and various organic hydroperoxides. Most of these species are involved in the regulation of cellular functions when formed at low, physiological levels. Additionally, they can cause oxidative damage when formed at higher rates, eventually leading to mitochondrial disfunction and cytotoxicity. Different peroxidases sense the levels and catalyze the reduction of mitochondrial hydroperoxides. Among them, peroxiredoxin 3 and peroxiredoxin 5 decompose most hydrogen peroxide, peroxynitrite and free fatty acid hydroperoxides formed in the mitochondrial matrix. Kinetic considerations indicate that the role of selenol-dependent glutathione peroxidases in the reduction of these soluble hydroperoxides in mitochondria would be secondary. Glutathione peroxidase 4, which has a unique phospholipid hydroperoxide peroxidase activity, is only expressed in the mitochondria of selected tissues. Peroxiredoxin 3 catalyzes the reduction of hydroperoxides, but is also hyperoxidized and inactivated by them, in particular by free fatty acid hydroperoxides which react at high rate constants. Indeed, computer-assisted simulations support that free fatty acid hydroperoxides significantly contribute to Prdx3 hyperoxidation under biologically-relevant conditions. In addition, kinetic data indicate that hydroperoxides may partially diffuse to the cytosol. Several open questions regarding the oxidizing substrate specificities of mitochondrial peroxiredoxins and their modulation by CO₂ are presented. Thus, peroxiredoxins 3 and 5 are the main sensors of mitochondrial hydroperoxides, provide protection from their excess and also determine the ability of these reactive species to diffuse through mitochondria; these combined actions of the mitochondrial peroxiredoxins impact redox regulation and outcomes of physiological or pathological processes.</p></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"5 ","pages":"Article 100017"},"PeriodicalIF":0.0,"publicationDate":"2023-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773176623000160/pdfft?md5=0b54038be7d1a0f97e7ca09df880b7b9&pid=1-s2.0-S2773176623000160-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134657763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular reductive stress: Is plasma membrane electron transport an evolutionarily-conserved safety valve?","authors":"M.V. Berridge ,&nbsp;P.M. Herst ,&nbsp;C. Prata","doi":"10.1016/j.rbc.2023.100016","DOIUrl":"https://doi.org/10.1016/j.rbc.2023.100016","url":null,"abstract":"<div><p>Cellular respiration is highly regulated, changes dynamically in response to the microenvironment of individual cells and during differentiation and differs between cell and tissue types. Too little cell respiration can cause an accumulation of reductants, leading to reductive stress, while inefficient respiration, that causes a build-up of reactive oxygen species (ROS), can result in oxidative stress. Most of the discussion of this central redox dichotomy has centred around oxidative stress because the damaging effects of cellular oxidants on DNA, lipids and proteins are well-established, and have been shown to contribute to health issues including, mitochondrial and cardiovascular diseases, tumorigenesis, and to the effects of ageing. Much less attention has been paid to cellular reductive stress. Nevertheless, excessive levels of key cellular reductants including NADH, NADPH and glutathione, as well as an imbalance in protein thiols, and insufficient levels of ROS to maintain cell signalling pathways, can be harmful to cells and result in poor health outcomes. Recently, cellular mechanisms that sense and regulate cellular reductive stress associated with low ROS levels have been identified. In addition, plasma membrane electron transport has been shown to be a key player in cellular redox homeostasis involving NAD(P)H/NAD(P)⁺ ratios. It is now well-established that the plasma membrane contains coenzyme Q-mediated electron transport pathways capable of oxidizing intracellular NAD(P)H and reducing extracellular electron acceptors such as molecular oxygen. A better understanding of the origins, cellular and subcellular compartmentalization and regulation of cellular reductants could lead to the development of new anticancer strategies.</p></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"5 ","pages":"Article 100016"},"PeriodicalIF":0.0,"publicationDate":"2023-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49754464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the enigmatic traits of Corynebacterium glutamicum mycoredoxin-3: A tiny redox protein displaying swapped homodimer formation and DsbA-like oxidase activity","authors":"Khadija Wahni ,&nbsp;Ekaterina Baranova ,&nbsp;Daria Ezeriņa ,&nbsp;Inge Van Molle ,&nbsp;Koen Van Laer ,&nbsp;Joris Messens","doi":"10.1016/j.rbc.2023.100014","DOIUrl":"https://doi.org/10.1016/j.rbc.2023.100014","url":null,"abstract":"<div><p>Mycoredoxins (Mrxs) are a group of small dithiol oxidoreductases that share a conserved CXXC active site sequence motif resembling glutaredoxins. They are commonly found in saprophytic microorganisms, including Actinobacteria such as <em>Mycobacterium tuberculosis</em>. Among the known mycoredoxins, <em>Corynebacterium glutamicum</em> (Cg) Mrx1, featuring a conserved CVQC active site, functions as a mycothiol-dependent monothiol oxidoreductase. On the other hand, Mrx2, also known as NrdH-redoxin and containing the same CVQC motif, exhibits dithiol oxidoreductase properties and receives electrons from thioredoxin reductase (TrxR). Recently, it has been reported that CgMrx3, featuring a CGSC motif, acts as a thioredoxin, although its structural and biophysical characteristics remain unexplored.</p><p>In this study, we successfully determined the X-ray structure of CgMrx3 at a resolution of 1.7 Å, revealing a swapped dimer arrangement. We compared the structure of CgMrx3 with those of CgMrx1 and CgMrx2 and with the AlphaFold2 predicted structure of Mrx3 from <em>Mycobaterium tuberculosis</em> (MtMrx3). We correlated the number of hydrogen bonds accepted by the nucleophilic cysteines with the relatively low pKa's determined for MtMrx3 and CgMrx3. Finally, we showed that CgMrx3 has DsbA-like oxidase activity. Taken together, our results provide valuable insights into the structural and functional characteristics of Mrx3, thereby enhancing our understanding of mycoredoxin-dependent redox biology.</p></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"5 ","pages":"Article 100014"},"PeriodicalIF":0.0,"publicationDate":"2023-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49726771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}