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Journal of Integrative Plant Biology Dec 2019Nitric oxide (NO) is an important signaling molecule regulating diverse biological processes in all living organisms. A major physiological function of NO is executed... (Review)
Review
Nitric oxide (NO) is an important signaling molecule regulating diverse biological processes in all living organisms. A major physiological function of NO is executed via protein S-nitrosylation, a redox-based posttranslational modification by covalently adding a NO molecule to a reactive cysteine thiol of a target protein. S-nitrosylation is an evolutionarily conserved mechanism modulating multiple aspects of cellular signaling. During the past decade, significant progress has been made in functional characterization of S-nitrosylated proteins in plants. Emerging evidence indicates that protein S-nitrosylation is ubiquitously involved in the regulation of plant development and stress responses. Here we review current understanding on the regulatory mechanisms of protein S-nitrosylation in various biological processes in plants and highlight key challenges in this field.
Topics: Nitric Oxide; Nitrosation; Plant Development; Plant Growth Regulators; Plant Proteins; Plants
PubMed: 30663237
DOI: 10.1111/jipb.12780 -
Current Opinion in Chemical Biology Aug 2023Protein S-glutathionylation is emerging as a central oxidation that regulates redox signaling and biological processes linked to diseases. In recent years, the field of... (Review)
Review
Protein S-glutathionylation is emerging as a central oxidation that regulates redox signaling and biological processes linked to diseases. In recent years, the field of protein S-glutathionylation has expanded by developing biochemical tools for the identification and functional analyses of S-glutathionylation, investigating knockout mouse models, and developing and evaluating chemical inhibitors for enzymes involved in glutathionylation. This review will highlight recent studies of two enzymes, glutathione transferase omega 1 (GSTO1) and glutaredoxin 1 (Grx1), especially introducing their glutathionylation substrates associated with inflammation, cancer, and neurodegeneration and showcasing the advancement of their chemical inhibitors. Lastly, we will feature protein substrates and chemical inducers of LanC-like protein (LanCL), the first enzyme in protein C-glutathionylation.
Topics: Animals; Mice; Glutathione; Protein S; Oxidation-Reduction; Protein Processing, Post-Translational; Biology
PubMed: 37245422
DOI: 10.1016/j.cbpa.2023.102326 -
Frontiers in Plant Science 2022Protein S-acylation, also known as palmitoylation, is an important lipid post-translational modification of proteins in eukaryotes. S-acylation plays critical roles in a... (Review)
Review
Protein S-acylation, also known as palmitoylation, is an important lipid post-translational modification of proteins in eukaryotes. S-acylation plays critical roles in a variety of protein functions involved in plant development and responses to abiotic and biotic stresses. The status of S-acylation on proteins is dynamic and reversible, which is catalyzed by protein S-acyltransferases (PATs) and reversed by acyl protein thioesterases. The cycle of S-acylation and de-S-acylation provides a molecular mechanism for membrane-associated proteins to undergo cycling and trafficking between different cell compartments and thus works as a switch to initiate or terminate particular signaling transductions on the membrane surface. In plants, thousands of proteins have been identified to be S-acylated through proteomics. Many S-acylated proteins and quite a few PAT-substrate pairs have been functionally characterized. A recently characterized acyl protein thioesterases family, ABAPT family proteins in , has provided new insights into the de-S-acylation process. However, our understanding of the regulatory mechanisms controlling the S-acylation and de-S-acylation process is surprisingly incomplete. In this review, we discuss how protein S-acylation level is regulated with the focus on catalyzing enzymes in plants. We also propose the challenges and potential developments for the understanding of the regulatory mechanisms controlling protein S-acylation in plants.
PubMed: 35968095
DOI: 10.3389/fpls.2022.956231 -
Journal of Medicinal Chemistry Apr 2022Protein -nitrosation (SNO), a posttranslational modification (PTM) of cysteine (Cys) residues elicited by nitric oxide (NO), regulates a wide range of protein functions.... (Review)
Review
Protein -nitrosation (SNO), a posttranslational modification (PTM) of cysteine (Cys) residues elicited by nitric oxide (NO), regulates a wide range of protein functions. As a crucial form of redox-based signaling by NO, SNO contributes significantly to the modulation of physiological functions, and SNO imbalance is closely linked to pathophysiological processes. Site-specific identification of the SNO protein is critical for understanding the underlying molecular mechanisms of protein function regulation. Although careful verification is needed, SNO modification data containing numerous functional proteins are a potential research direction for druggable target identification and drug discovery. Undoubtedly, SNO-related research is meaningful not only for the development of NO donor drugs but also for classic target-based drug design. Herein, we provide a comprehensive summary of SNO, including its origin and transport, identification, function, and potential contribution to drug discovery. Importantly, we propose new views to develop novel therapies based on potential protein SNO-sourced targets.
Topics: Cysteine; Nitric Oxide; Nitrosation; Protein Processing, Post-Translational; Protein S; Proteins
PubMed: 35412827
DOI: 10.1021/acs.jmedchem.1c02194 -
Journal of Medicine and Life Nov 2022This study was conducted to assess the level of proteins C and S in patients with thalassemia intermedia from the Thalassemia Center in Erbil, Iraq. This study aimed to...
This study was conducted to assess the level of proteins C and S in patients with thalassemia intermedia from the Thalassemia Center in Erbil, Iraq. This study aimed to evaluate protein C and S levels in patients with β-thalassemia intermedia and correlate them to different clinical and laboratory parameters. This comprehensive descriptive case-control study was conducted in 2021. Twenty-three thalassemia intermedia patients were recruited. After the participants' demographic data were recorded, plasma levels of both proteins were measured. The acquired files were examined for the 23 patients studied, 48% of whom were female. The mean age of the patients was 16.32 years. The findings show that the proportion of protein C in males was greater than in females, while this percentage contrasts when compared with protein S (ranging between 89-99% and 85-96%, respectively). Concerning age, these two types of protein in children have more value compared to older ages. Only seven people had less than 1,000 ferritins, while the others had higher values. A decrease in proteins C and S was observed in the thalassemia intermediate compared to the control group. There was a significant relationship between the decreased protein C and S levels with splenectomy. Given the significant reduction in protein C and S levels among patients with thalassemia intermediate compared to the control group, there is an increased risk of thromboembolic events in patients with thalassemia intermediate.
Topics: Adolescent; Child; Female; Humans; Male; beta-Thalassemia; Case-Control Studies; Ferritins; Protein C; Protein S; Thromboembolism
PubMed: 36567848
DOI: 10.25122/jml-2021-0316 -
British Journal of Pharmacology Feb 2020Hydrogen sulfide (H S) is a signalling molecule that regulates neuronal transmission, vascular tone, cytoprotection, inflammatory responses, angiogenesis, and oxygen... (Review)
Review
Hydrogen sulfide (H S) is a signalling molecule that regulates neuronal transmission, vascular tone, cytoprotection, inflammatory responses, angiogenesis, and oxygen sensing. Some of these functions have recently been ascribed to its oxidized form polysulfides (H S ), which can be produced by 3-mercaptopyruvate sulfurtransferase (MPST), also known as a H S-producing enzyme. H S activate ion channels, tumour suppressors, transcription factors, and protein kinases. H S S-sulfurate (S-sulfhydrate) cysteine residues of these target proteins to modify their activity by inducing conformational changes through the formation of a disulfide bridge between the two cysteine residues involved. The chemical interaction between H S and NO also generates H S , which may be a chemical entity that exerts the synergistic effect of H S and NO. MPST also produces redox regulators cysteine persulfide (CysSSH), GSH persulfide (GSSH), and persulfurated proteins. In addition to MPST, haemoproteins such as haemoglobin, myoglobin, neuroglobin, and catalase as well as SOD can produce H S , and sulfide quinone oxidoreductase and cysteinyl tRNA synthetase can make GSSH and CysSSH. This review focuses on the recent progress in the study of the production and physiological roles of these persulfurated and polysulfurated molecules. LINKED ARTICLES: This article is part of a themed section on Hydrogen Sulfide in Biology & Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.4/issuetoc.
Topics: Hydrogen Sulfide; Protein S; Signal Transduction; Sulfides
PubMed: 30657595
DOI: 10.1111/bph.14579 -
Frontiers in Immunology 2024Protein S-palmitoylation is a reversible post-translational lipid modification that involves the addition of a 16-carbon palmitoyl group to a protein cysteine residue... (Review)
Review
Protein S-palmitoylation is a reversible post-translational lipid modification that involves the addition of a 16-carbon palmitoyl group to a protein cysteine residue via a thioester linkage. This modification plays a crucial role in the regulation protein localization, accumulation, secretion, stability, and function. Dysregulation of protein S-palmitoylation can disrupt cellular pathways and contribute to the development of various diseases, particularly cancers. Aberrant S-palmitoylation has been extensively studied and proven to be involved in tumor initiation and growth, metastasis, and apoptosis. In addition, emerging evidence suggests that protein S-palmitoylation may also have a potential role in immune modulation. Therefore, a comprehensive understanding of the regulatory mechanisms of S-palmitoylation in tumor cells and the tumor immune microenvironment is essential to improve our understanding of this process. In this review, we summarize the recent progress of S-palmitoylation in tumors and the tumor immune microenvironment, focusing on the S-palmitoylation modification of various proteins. Furthermore, we propose new ideas for immunotherapeutic strategies through S-palmitoylation intervention.
Topics: Humans; Lipoylation; Protein Processing, Post-Translational; Cysteine; Neoplasms; Tumor Microenvironment
PubMed: 38415253
DOI: 10.3389/fimmu.2024.1337478 -
Platelets Dec 2024Protein S (PS) is a vital endogenous anticoagulant. It plays a crucial role in regulating coagulation by acting as a cofactor for the activated protein C (APC) and... (Review)
Review
Protein S (PS) is a vital endogenous anticoagulant. It plays a crucial role in regulating coagulation by acting as a cofactor for the activated protein C (APC) and tissue factor pathway inhibitor (TFPI) pathways. Additionally, it possesses direct anticoagulant properties by impeding the intrinsic tenase and prothrombinase complexes. Protein S oversees the coagulation process in both the initiation and propagation stages through these roles. The significance of protein S in regulating blood clotting can be inferred from the significant correlation between deficits in protein S and an elevated susceptibility to venous thrombosis. This is likely because activated protein C and tissue factor pathway inhibitor exhibit low efficacy as anticoagulants when no cofactors exist. The precise biochemical mechanisms underlying the roles of protein S cofactors have yet to be fully elucidated. Nevertheless, recent scientific breakthroughs have significantly enhanced comprehension findings for these functions. The diagnosis of protein S deficiency, both from a technical and genetic standpoint, is still a subject of debate due to the complex structural characteristics of the condition. This paper will provide an in-depth review of the molecular structure of protein S and its hemostatic effects. Furthermore, we shall address the insufficiency of protein S and its methods of diagnosis and treatment.
Topics: Humans; Anticoagulants; Protein C; Blood Coagulation; Hemostatics
PubMed: 38602463
DOI: 10.1080/09537104.2024.2337907 -
Life (Basel, Switzerland) Jul 2021Abnormal and excessive nitrosative stress contributes to neurodegenerative disease associated with the production of pathological levels of misfolded proteins. The... (Review)
Review
Abnormal and excessive nitrosative stress contributes to neurodegenerative disease associated with the production of pathological levels of misfolded proteins. The accumulated findings strongly suggest that excessive NO production can induce and deepen these pathological processes, particularly by the S-nitrosylation of target proteins. Therefore, the relationship between S-nitrosylated proteins and the accumulation of misfolded proteins was reviewed. We particularly focused on the S-nitrosylation of E3-ubiquitin-protein ligase, parkin, and endoplasmic reticulum chaperone, PDI, which contribute to the accumulation of misfolded proteins. In addition to the target proteins being S-nitrosylated, NOS, which produces NO, and GSNOR, which inhibits S-nitrosylation, were also suggested as potential therapeutic targets for protein misfolding-associated diseases.
PubMed: 34357077
DOI: 10.3390/life11070705 -
Computers in Biology and Medicine Sep 2023S-sulfenylation is a vital post-translational modification (PTM) of proteins, which is an intermediate in other redox reactions and has implications for signal...
S-sulfenylation is a vital post-translational modification (PTM) of proteins, which is an intermediate in other redox reactions and has implications for signal transduction and protein function regulation. However, there are many restrictions on the experimental identification of S-sulfenylation sites. Therefore, predicting S-sulfoylation sites by computational methods is fundamental to studying protein function and related biological mechanisms. In this paper, we propose a method named BiGRUD-SA based on bi-directional gated recurrent unit (BiGRU) and self-attention mechanism to predict protein S-sulfenylation sites. We first use AAC, BLOSUM62, AAindex, EAAC and GAAC to extract features, and do feature fusion to obtain original feature space. Next, we use SMOTE-Tomek method to handle data imbalance. Then, we input the processed data to the BiGRU and use self-attention mechanism to do further feature extraction. Finally, we input the data obtained to the deep neural networks (DNN) to identify S-sulfenylation sites. The accuracies of training set and independent test set are 96.66% and 95.91% respectively, which indicates that our method is conducive to identifying S-sulfenylation sites. Furthermore, we use a data set of S-sulfenylation sites in Arabidopsis thaliana to effectively verify the generalization ability of BiGRUD-SA method, and obtain better prediction results.
Topics: Protein S; Computational Biology; Support Vector Machine; Proteins; Protein Processing, Post-Translational; Arabidopsis
PubMed: 37336062
DOI: 10.1016/j.compbiomed.2023.107145