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3 pages, 188 KiB

Open AccessEditorial

Redox Regulation of Protein Functioning

by Andrey A. Zamyatnin, Jr.

Biomolecules 2023, 13(9), 1281; https://doi.org/10.3390/biom13091281 - 22 Aug 2023

Viewed by 786

Abstract

Reactive oxygen species (ROS) and their derivatives play a key role in signaling under normal and oxidative stress conditions in all aerobic living organisms [...] Full article

(This article belongs to the Special Issue Redox Regulation of Protein Functioning)

Research

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20 pages, 2697 KiB

Open AccessArticle

Redox Regulation of Signaling Complex between Caveolin-1 and Neuronal Calcium Sensor Recoverin

by Vasiliy I. Vladimirov, Margarita P. Shchannikova, Alexey V. Baldin, Alexey S. Kazakov, Marina P. Shevelyova, Aliya A. Nazipova, Viktoriia E. Baksheeva, Ekaterina L. Nemashkalova, Anastasia S. Frolova, Natalia K. Tikhomirova, Pavel P. Philippov, Andrey A. Zamyatnin, Jr., Sergei E. Permyakov, Dmitry V. Zinchenko and Evgeni Yu. Zernii

Biomolecules 2022, 12(11), 1698; https://doi.org/10.3390/biom12111698 - 16 Nov 2022

Cited by 1 | Viewed by 1831

Abstract

Caveolin-1 is a cholesterol-binding scaffold protein, which is localized in detergent-resistant membrane (DRM) rafts and interacts with components of signal transduction systems, including visual cascade. Among these components are neuronal calcium sensors (NCSs), some of which are redox-sensitive proteins that respond to calcium [...] Read more.

Caveolin-1 is a cholesterol-binding scaffold protein, which is localized in detergent-resistant membrane (DRM) rafts and interacts with components of signal transduction systems, including visual cascade. Among these components are neuronal calcium sensors (NCSs), some of which are redox-sensitive proteins that respond to calcium signals by modulating the activity of multiple intracellular targets. Here, we report that the formation of the caveolin-1 complex with recoverin, a photoreceptor NCS serving as the membrane-binding regulator of rhodopsin kinase (GRK1), is a redox-dependent process. Biochemical and biophysical in vitro experiments revealed a two-fold decreased affinity of recoverin to caveolin-1 mutant Y14E mimicking its oxidative stress-induced phosphorylation of the scaffold protein. At the same time, wild-type caveolin-1 demonstrated a 5–10-fold increased affinity to disulfide dimer of recoverin (dRec) or its thiol oxidation mimicking the C39D mutant. The formation of dRec in vitro was not affected by caveolin-1 but was significantly potentiated by zinc, the well-known mediator of redox homeostasis. In the MDCK cell model, oxidative stress indeed triggered Y14 phosphorylation of caveolin-1 and disulfide dimerization of recoverin. Notably, oxidative conditions promoted the accumulation of phosphorylated caveolin-1 in the plasma membrane and the recruitment of recoverin to the same sites. Co-localization of these proteins was preserved upon depletion of intracellular calcium, i.e., under conditions reducing membrane affinity of recoverin but favoring its interaction with caveolin-1. Taken together, these data suggest redox regulation of the signaling complex between recoverin and caveolin-1. During oxidative stress, the high-affinity interaction of thiol-oxidized recoverin with caveolin-1/DRMs may disturb the light-induced translocation of the former within photoreceptors and affect rhodopsin desensitization. Full article

(This article belongs to the Special Issue Redox Regulation of Protein Functioning)

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23 pages, 58767 KiB

Open AccessArticle

Design, Synthesis, Kinetic Analysis and Pharmacophore-Directed Discovery of 3-Ethylaniline Hybrid Imino-Thiazolidinone as Potential Inhibitor of Carbonic Anhydrase II: An Emerging Biological Target for Treatment of Cancer

by Atteeque Ahmed, Mubashir Aziz, Syeda Abida Ejaz, Pervaiz Ali Channar, Aamer Saeed, Seema Zargar, Tanveer A. Wani, Asad Hamad, Qamar Abbas, Hussain Raza and Song Ja Kim

Biomolecules 2022, 12(11), 1696; https://doi.org/10.3390/biom12111696 - 16 Nov 2022

Cited by 9 | Viewed by 2093

Abstract

Carbonic anhydrases (CA), having Zn²⁺ metal atoms, are responsible for the catalysis of CO₂ and water to bicarbonate and protons. Any abnormality in the functioning of these enzymes may lead to morbidities such as glaucoma and different types of cancers including [...] Read more.

Carbonic anhydrases (CA), having Zn²⁺ metal atoms, are responsible for the catalysis of CO₂ and water to bicarbonate and protons. Any abnormality in the functioning of these enzymes may lead to morbidities such as glaucoma and different types of cancers including brain, renal and pancreatic carcinomas. To cope with the lack of presence of a promising therapeutic agent against these cancers, searching for an efficient and suitable carbonic anhydrase inhibitor is crucial. In the current study, ten novel 3-ethylaniline hybrid imino-thiazolidinones were synthesized and characterized by FTIR, NMR (¹H, ¹³C), and mass spectrometry. Synthesis was carried out by diethyl but-2-ynedioate cyclization and different acyl thiourea substitutions of 3-ethyl amine. The CA (II) enzyme inhibition profile for all synthesized derivatives was determined. It was observed that compound 6e demonstrated highest inhibition of CA-II with an IC₅₀ value of 1.545 ± 0.016 µM. In order to explore the pharmacophoric properties and develop structure activity relationship, in silico screening was performed. In silico investigations included density functional theory (DFT) studies, pharmacophore-guided model development, molecular docking, molecular dynamic (MD) simulations, and prediction of drug likeness scores. DFT investigations provided insight into the electronic characteristics of compounds, while molecular docking determined the binding orientation of derivatives within the CA-II active site. Compounds 6a, 6e, and 6g had a reactive profile and generated stable protein-ligand interactions with respective docking scores of −6.12, −6.99, and −6.76 kcal/mol. MD simulations were used to evaluate the stability of the top-ranked complex. In addition, pharmacophore-guided modeling demonstrated that compound 6e produced the best pharmacophore model (HHAAARR) compared to standard brinzolamide. In vitro and in silico investigations anticipated that compound 6e would be an inhibitor of carbonic anhydrase II with high efficacy. Compound 6e may serve as a potential lead for future synthesis that can be investigated at the molecular level, and additional in vivo studies are strongly encouraged. Full article

(This article belongs to the Special Issue Redox Regulation of Protein Functioning)

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10 pages, 1000 KiB

Open AccessArticle

Cysteine Oxidation Promotes Dimerization/Oligomerization of Circadian Protein Period 2

by Fernando Martin Baidanoff, Laura Lucía Trebucq, Santiago Andrés Plano, Phillip Eaton, Diego Andrés Golombek and Juan José Chiesa

Biomolecules 2022, 12(7), 892; https://doi.org/10.3390/biom12070892 - 25 Jun 2022

Cited by 2 | Viewed by 2151

Abstract

The molecular circadian clock is based on a transcriptional/translational feedback loop in which the stability and half-life of circadian proteins is of importance. Cysteine residues of proteins are subject to several redox reactions leading to S-thiolation and disulfide bond formation, altering protein stability [...] Read more.

The molecular circadian clock is based on a transcriptional/translational feedback loop in which the stability and half-life of circadian proteins is of importance. Cysteine residues of proteins are subject to several redox reactions leading to S-thiolation and disulfide bond formation, altering protein stability and function. In this work, the ability of the circadian protein period 2 (PER2) to undergo oxidation of cysteine thiols was investigated in HEK-293T cells. PER2 includes accessible cysteines susceptible to oxidation by nitroso cysteine (CysNO), altering its stability by decreasing its monomer form and subsequently increasing PER2 homodimers and multimers. These changes were reversed by treatment with 2-mercaptoethanol and partially mimicked by hydrogen peroxide. These results suggest that cysteine oxidation can prompt PER2 homodimer and multimer formation in vitro, likely by S-nitrosation and disulphide bond formation. These kinds of post-translational modifications of PER2 could be part of the redox regulation of the molecular circadian clock. Full article

(This article belongs to the Special Issue Redox Regulation of Protein Functioning)

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13 pages, 5740 KiB

Open AccessArticle

Overexpression of Banana ATG8f Modulates Drought Stress Resistance in Arabidopsis

by Bing Li, Guoyin Liu, Yuqi Wang, Yunxie Wei and Haitao Shi

Biomolecules 2019, 9(12), 814; https://doi.org/10.3390/biom9120814 - 2 Dec 2019

Cited by 26 | Viewed by 3377

Abstract

Autophagy is essential for plant growth, development, and stress resistance. However, the involvement of banana autophagy-related genes in drought stress response and the underlying mechanism remain elusive. In this study, we found that the transcripts of 10 banana ATG8s responded to drought stress [...] Read more.

Autophagy is essential for plant growth, development, and stress resistance. However, the involvement of banana autophagy-related genes in drought stress response and the underlying mechanism remain elusive. In this study, we found that the transcripts of 10 banana ATG8s responded to drought stress in different ways, and MaATG8f with the highest transcript in response to drought stress among them was chosen for functional analysis. Overexpression of MaATG8f improved drought stress resistance in Arabidopsis, with lower malonaldehyde level and higher level of assimilation rate. On the one hand, overexpression of MaATG8f activated the activities of superoxide dismutase, catalase, and peroxidase under drought stress conditions, so as to regulate reactive oxygen species accumulation. On the other hand, MaATG8f-overexpressing lines exhibited higher endogenous abscisic acid (ABA) level and more sensitivity to abscisic acid. Notably, the autophagosomes as visualized by CaMV35S::GFP–MaATG8f was activated after ABA treatment. Taken together, overexpression of MaATG8f positively regulated plant drought stress resistance through modulating reactive oxygen species metabolism, abscisic acid biosynthesis, and autophagic activity. Full article

(This article belongs to the Special Issue Redox Regulation of Protein Functioning)

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22 pages, 5434 KiB

Open AccessArticle

Tomato Root Growth Inhibition by Salinity and Cadmium is Mediated by S-Nitrosative Modifications of ROS Metabolic Enzymes Controlled by S-Nitrosoglutathione Reductase

by Tereza Jedelská, Veronika Šmotková Kraiczová, Lucie Berčíková, Lucie Činčalová, Lenka Luhová and Marek Petřivalský

Biomolecules 2019, 9(9), 393; https://doi.org/10.3390/biom9090393 - 21 Aug 2019

Cited by 19 | Viewed by 3638

Abstract

S-nitrosoglutathione reductase (GSNOR) exerts crucial roles in the homeostasis of nitric oxide (NO) and reactive nitrogen species (RNS) in plant cells through indirect control of S-nitrosation, an important protein post-translational modification in signaling pathways of NO. Using cultivated and wild tomato species, we [...] Read more.

S-nitrosoglutathione reductase (GSNOR) exerts crucial roles in the homeostasis of nitric oxide (NO) and reactive nitrogen species (RNS) in plant cells through indirect control of S-nitrosation, an important protein post-translational modification in signaling pathways of NO. Using cultivated and wild tomato species, we studied GSNOR function in interactions of key enzymes of reactive oxygen species (ROS) metabolism with RNS mediated by protein S-nitrosation during tomato root growth and responses to salinity and cadmium. Application of a GSNOR inhibitor N6022 increased both NO and S-nitrosothiol levels and stimulated root growth in both genotypes. Moreover, N6022 treatment, as well as S-nitrosoglutathione (GSNO) application, caused intensive S-nitrosation of important enzymes of ROS metabolism, NADPH oxidase (NADPHox) and ascorbate peroxidase (APX). Under abiotic stress, activities of APX and NADPHox were modulated by S-nitrosation. Increased production of H₂O₂ and subsequent oxidative stress were observed in wild Solanum habrochaites, together with increased GSNOR activity and reduced S-nitrosothiols. An opposite effect occurred in cultivated S. lycopersicum, where reduced GSNOR activity and intensive S-nitrosation resulted in reduced ROS levels by abiotic stress. These data suggest stress-triggered disruption of ROS homeostasis, mediated by modulation of RNS and S-nitrosation of NADPHox and APX, underlies tomato root growth inhibition by salinity and cadmium stress. Full article

(This article belongs to the Special Issue Redox Regulation of Protein Functioning)

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Review

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27 pages, 2469 KiB

Open AccessReview

Redox Impact on Bacterial Macromolecule: A Promising Avenue for Discovery and Development of Novel Antibacterials

by Jamiu Olaseni Aribisala and Saheed Sabiu

Biomolecules 2022, 12(11), 1545; https://doi.org/10.3390/biom12111545 - 22 Oct 2022

Cited by 10 | Viewed by 1837

Abstract

Antibiotic resistance in bacteria has remained a serious public health concern, resulting in substantial deaths and morbidity each year. Factors such as mutation and abuse of currently available antibiotics have contributed to the bulk of the menace. Hence, the introduction and implementation of [...] Read more.

Antibiotic resistance in bacteria has remained a serious public health concern, resulting in substantial deaths and morbidity each year. Factors such as mutation and abuse of currently available antibiotics have contributed to the bulk of the menace. Hence, the introduction and implementation of new therapeutic strategies are imperative. Of these strategies, data supporting the role of reactive oxygen species (ROS) in bacterial lethality are intriguing, with several antimicrobials, including antibiotics such as fluoroquinolones, β-lactams, and aminoglycosides, as well as natural plant compounds, being remarkably implicated. Following treatment with ROS-inducing antimicrobials, ROS such as O₂^•−, ^•OH, and H₂O₂ generated in bacteria, which the organism is unable to detoxify, damage cellular macromolecules such as proteins, lipids, and nucleic acids and results in cell death. Despite the unique mechanism of action of ROS-inducing antibacterials and significant studies on ROS-mediated means of bacterial killing, the field remains a topical one, with contradicting viewpoints that require frequent review. Here, we appraised the antibacterial agents (antibiotics, natural and synthetic compounds) implicated in ROS generation and the safety concerns associated with their usage. Further, background information on the sources and types of ROS in bacteria, the mechanism of bacterial lethality via oxidative stress, as well as viewpoints on the ROS hypothesis undermining and solidifying this concept are discussed. Full article

(This article belongs to the Special Issue Redox Regulation of Protein Functioning)

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22 pages, 681 KiB

Open AccessReview

Redox-Mediated Post-Translational Modifications of Proteolytic Enzymes and Their Role in Protease Functioning

by Anastasiia I. Petushkova and Andrey A. Zamyatnin, Jr.

Biomolecules 2020, 10(4), 650; https://doi.org/10.3390/biom10040650 - 23 Apr 2020

Cited by 20 | Viewed by 3720

Abstract

Proteolytic enzymes play a crucial role in metabolic processes, providing the cell with amino acids through the hydrolysis of multiple endogenous and exogenous proteins. In addition to this function, proteases are involved in numerous protein cascades to maintain cellular and extracellular homeostasis. The [...] Read more.

Proteolytic enzymes play a crucial role in metabolic processes, providing the cell with amino acids through the hydrolysis of multiple endogenous and exogenous proteins. In addition to this function, proteases are involved in numerous protein cascades to maintain cellular and extracellular homeostasis. The redox regulation of proteolysis provides a flexible dose-dependent mechanism for proteolytic activity control. The excessive reactive oxygen species (ROS) and reactive nitrogen species (RNS) in living organisms indicate pathological conditions, so redox-sensitive proteases can swiftly induce pro-survival responses or regulated cell death (RCD). At the same time, severe protein oxidation can lead to the dysregulation of proteolysis, which induces either protein aggregation or superfluous protein hydrolysis. Therefore, oxidative stress contributes to the onset of age-related dysfunction. In the present review, we consider the post-translational modifications (PTMs) of proteolytic enzymes and their impact on homeostasis. Full article

(This article belongs to the Special Issue Redox Regulation of Protein Functioning)

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