PGluS: prediction of protein S-glutathionylation sites with multiple features and analysis

2015 ◽  
Vol 11 (3) ◽  
pp. 923-929 ◽  
Author(s):  
Xiaowei Zhao ◽  
Qiao Ning ◽  
Meiyu Ai ◽  
Haiting Chai ◽  
Minghao Yin
Keyword(s):  
Protein Stability ◽  
Redox Regulation ◽  
Protein S ◽  
Cysteine Residues ◽  
Post Translational Modification ◽  
Multiple Features ◽  
Mixed Disulfides

S-Glutathionylation is a reversible protein post-translational modification, which generates mixed disulfides between glutathione (GSH) and cysteine residues, playing an important role in regulating protein stability, activity, and redox regulation.

scholarly journals Redox Regulation by Protein S-Glutathionylation: From Molecular Mechanisms to Implications in Health and Disease

2020 ◽  
Vol 21 (21) ◽  
pp. 8113 ◽  
Author(s):  
Aysenur Musaogullari ◽  
Yuh-Cherng Chai
Keyword(s):  
Protein Function ◽  
Liver Diseases ◽  
Redox Regulation ◽  
Molecular Mechanisms ◽  
Protein S ◽  
Protective Mechanism ◽  
Post Translational Modification ◽  
Physiological Processes ◽  
Health And Disease ◽  
Mixed Disulfides

S-glutathionylation, the post-translational modification forming mixed disulfides between protein reactive thiols and glutathione, regulates redox-based signaling events in the cell and serves as a protective mechanism against oxidative damage. S-glutathionylation alters protein function, interactions, and localization across physiological processes, and its aberrant function is implicated in various human diseases. In this review, we discuss the current understanding of the molecular mechanisms of S-glutathionylation and describe the changing levels of expression of S-glutathionylation in the context of aging, cancer, cardiovascular, and liver diseases.

Abstract 223: S-glutathiolation Uncouples Endothelial Nitric Oxide (NO) Synthase, Switching Enzyme from NO to Superoxide Production

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Chun-An Chen ◽  
Lawrence J Druhan ◽  
Tse-Yao Wang ◽  
Yeong-Renn Chen ◽  
Jay L Zweier
Keyword(s):  
Oxidative Stress ◽  
Protein Modification ◽  
Redox Regulation ◽  
Cardiovascular Function ◽  
Heart Association ◽  
Protein S ◽  
No Production ◽  
Protein Thiols ◽  
Mixed Disulfides ◽  
Endothelial Nitric Oxide

Overproduction of superoxide (•O 2 − ) and •O 2 − -derived oxidants increases cellular oxidative stress. This can lead to cell death, via apoptosis or necrosis. An important response of protein thiols to oxidative stress is reversible formation of protein mixed disulfides via S-glutathiolation. This redox based protein modification is thought to play an important role as an adaptive response to oxidative injury in cells, or alternatively in controlling cellular signaling in a manner similar to phosphorylation. Protein S-glutathiolation is increased in the post-ischemic heart. Human eNOS, which is of critical importance in maintaining cardiovascular function, contains 29 cysteinyl residues. To investigate the effects of S-glutathiolation on the regulation of eNOS function and its relation to cardiovascular diseases, eNOS functional alterations induced by S-glutathiolation were studied. Additionally, LC/MS/MS was used to determine the precise residues of eNOS involved in this redox-dependent thiol modification. S-glutatiolation significantly reduced NO production from heNOS, with a 63% decrease induced by incubation with 2 mM GSSG in vitro . This process was reversible by addition of DTT. Alkylation of the cysteinyl residues with N-ethylmaleimide (NEM) completely inhibited NO production. S-glutathiolation of an uncoupled heNOS increased •O 2 − generation (> 70%), and this increase was only partially blocked by L-NAME, implicating the reductase site as the source for the increased •O 2 − generation. When the cysteinyl residues were all alkylated with NEM, the •O 2 − generation from eNOS was dramatically increased (+2.4-fold), and this increase was not inhibited by L-NAME. We have identified three cysteine residues, C 382 , C 689 and C 908 as sights of S-glutathiolation in heNOS, all three of which are conserved in all known mammalian eNOS enzymes. Therefore, cysteinyl residues are critical for the regulation of eNOS coupling, and S-glutatiolation of specific residues switches eNOS from an NO producing to a •O 2 − generating enzyme, by inducing electron leakage from the reductase domain. As such, S-glutathiolation provides a novel mechanism for the regulation of heNOS, defining a unique pathway for the redox regulation of cardiovascular function. This research has received full or partial funding support from the American Heart Association, AHA Great Rivers Affiliate (Delaware, Kentucky, Ohio, Pennsylvania & West Virginia).

scholarly journals The Role of Cysteine Residues in Redox Regulation and Protein Stability of Arabidopsis thaliana Starch Synthase 1

PLoS ONE ◽  
2015 ◽  
Vol 10 (9) ◽  
pp. e0136997 ◽  
Author(s):  
Katsiaryna Skryhan ◽  
Jose A. Cuesta-Seijo ◽  
Morten M. Nielsen ◽  
Lucia Marri ◽  
Silas B. Mellor ◽  
...  
Keyword(s):  
Arabidopsis Thaliana ◽  
Protein Stability ◽  
Redox Regulation ◽  
Starch Synthase ◽  
Cysteine Residues

scholarly journals The gene encoding vitamin K-dependent anticoagulant protein C is expressed in human male reproductive tissues.

1995 ◽  
Vol 43 (6) ◽  
pp. 563-570 ◽  
Author(s):  
X He ◽  
L Shen ◽  
A Bjartell ◽  
J Malm ◽  
H Lilja ◽  
...  
Keyword(s):  
Vitamin K ◽  
Leydig Cells ◽  
Protein C ◽  
Protein S ◽  
Northern Blotting ◽  
Human Testis ◽  
Post Translational Modification ◽  
Reproductive Tissues ◽  
Human Male ◽  
Dependent Protein

Protein C is a vitamin K-dependent protein circulating in plasma as a zymogen to an anticoagulant serine protease. After its activation, protein C cleaves and inactivates coagulation factors Va and VIIIa. Human protein C is synthesized in liver and undergoes extensive post-translational modification during its synthesis. Recently, the protein C inhibitor was demonstrated to be synthesized in several organs of the human male reproductive tract. Moreover, vitamin K-dependent protein S, which functions as a co-factor to activated protein C, was found to be synthesized in the Leydig cells of human testis. The aim of this study was to elucidate whether the protein C gene is also expressed in the male reproductive system. Specific immunostaining of protein C was found in Leydig cells of human testis, in the excretory epithelium of epididymis, and in some epithelial glands of the prostate, whereas no immunostaining was detected in seminal vesicles. Northern blotting and non-radioactive in situ hybridization demonstrated protein C mRNA in Leydig cells, in the excretory epithelium of epididymis, and in some of the epithelial glands of the prostate. The mRNA was distributed perinuclearly and the localization was in accordance with the specific immunostaining for protein C. The epithelium of epididymis was also found to contain both protein S mRNA and immunoreactivity. The demonstration of both protein C and protein S immunoreactivities, as well as their mRNAs, in male reproductive tissues suggests as yet unknown local functions for these proteins.

scholarly journals A computational in silico approach to predict high-risk coding and non-coding SNPs of human PLCG1 gene

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0260054
Author(s):  
Safayat Mahmud Khan ◽  
Ar-Rafi Md. Faisal ◽  
Tasnin Akter Nila ◽  
Nabila Nawar Binti ◽  
Md. Ismail Hosen ◽  
...  
Keyword(s):  
Protein Structure ◽  
T Cell ◽  
Protein Stability ◽  
In Silico ◽  
Catalytic Domain ◽  
Cell Lymphoma ◽  
Computational Study ◽  
Solvent Accessibility ◽  
T Cell Lymphoma ◽  
Post Translational Modification

PLCG1 gene is responsible for many T-cell lymphoma subtypes, including peripheral T-cell lymphoma (PTCL), angioimmunoblastic T-cell lymphoma (AITL), cutaneous T-cell lymphoma (CTCL), adult T-cell leukemia/lymphoma along with other diseases. Missense mutations of this gene have already been found in patients of CTCL and AITL. The non-synonymous single nucleotide polymorphisms (nsSNPs) can alter the protein structure as well as its functions. In this study, probable deleterious and disease-related nsSNPs in PLCG1 were identified using SIFT, PROVEAN, PolyPhen-2, PhD-SNP, Pmut, and SNPS&GO tools. Further, their effect on protein stability was checked along with conservation and solvent accessibility analysis by I-mutant 2.0, MUpro, Consurf, and Netsurf 2.0 server. Some SNPs were finalized for structural analysis with PyMol and BIOVIA discovery studio visualizer. Out of the 16 nsSNPs which were found to be deleterious, ten nsSNPs had an effect on protein stability, and six mutations (L411P, R355C, G493D, R1158H, A401V and L455F) were predicted to be highly conserved. Among the six highly conserved mutations, four nsSNPs (R355C, A401V, L411P and L455F) were part of the catalytic domain. L411P, L455F and G493D made significant structural change in the protein structure. Two mutations-Y210C and R1158H had post-translational modification. In the 5’ and 3’ untranslated region, three SNPs, rs139043247, rs543804707, and rs62621919 showed possible miRNA target sites and DNA binding sites. This in silico analysis has provided a structured dataset of PLCG1 gene for further in vivo researches. With the limitation of computational study, it can still prove to be an asset for the identification and treatment of multiple diseases associated with the target gene.

Abstract 15523: Dynamic Protein S-palmitoylation Contributes to Cardiac Remodeling During Aging With Chronic Hypertension

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Madeleine R Miles ◽  
John Seo ◽  
Zachary Wilson ◽  
Min Jiang ◽  
Gea-ny Tseng
Keyword(s):  
Heart Failure ◽  
Protein Function ◽  
Ventricular Myocytes ◽  
Wide Spectrum ◽  
Enrichment Analysis ◽  
Protein S ◽  
Ventricular Myocardium ◽  
Chronic Hypertension ◽  
Post Translational Modification ◽  
Α Subunit

Introduction: More that 10% of human proteins can be S-palmitoylated, a post-translational modification (PTM) whereby palmitoyl chains are covalently linked to cysteine thiol groups. S-palmitoylation influences protein trafficking, distribution and function. There is no information on the scope of protein S-palmitoylation in the heart, or how this enzyme-mediated reversible PTM is regulated. Hypothesis: S-palmitoylation occurs to a wide spectrum of proteins in cardiomyocytes, and is coordinated by membrane-embedded palmitoylating (DHHC) enzymes. DHHC enzymes are subject to remodeling during chronic hypertension. Methods: We used resin-assisted capture to purify S-palmitoylated proteins from ventricular myocardium of 3 species: human, dog, and rat. We used global unbiased proteomic search to identify S-palmitoylated proteins. We validated DHHC antibodies and used them to monitor protein level and subcellular distribution of native DHHC enzymes in ventricular myocytes. Results: We built a 'composite' cardiac palmitome composed of 462 S-palmitoylatable proteins identified in ≥ 2 species-specific cardiac palmitomes. Enrichment analysis based on GO term 'cellular component' indicated that they are mainly involved in cell-cell and cell-substrate associations, sarcolemma and sarcomere organization, vesicular trafficking, G-protein function, ATP-dependent transmembrane transport, and mitochondria inner and outer membrane organization. Among the 23 DHHC enzymes, we detected ten in hearts across species. In ventricular myocytes with well-defined subcellular compartments, DHHC enzymes exhibited distinct distribution patterns: peripheral sarcolemma (DHHC1), M-lines (DHHC2), Z-lines (DHHC5), vesicles (DHHC7) and intercalated disc (DHHC9). In aging spontaneously hypertensive rats (a model of chronic hypertension, some in heart failure), seven DHHC enzymes were upregulated in the heart, accompanied by a higher degree of S-palmitoylation of CaMK II, caveolin3, Na/Ca exchanger, and Na/K pump α-subunit. Conclusion: S-palmitoylation is involved in most, if not all, aspects of cardiomyocyte function. Palmitoylation dysregulation may contribute to pathological progression in hypertrophy leading to heart failure.

scholarly journals Antioxidant Properties of S-Nitrosoglutathione and Nanotechnologies

Proceedings ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 15
Author(s):  
Parent ◽  
Zhou ◽  
Bonetti ◽  
Perrin-Sarrado ◽  
Lartaud ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Cardiovascular Diseases ◽  
Sustained Release ◽  
Antioxidant Properties ◽  
Protein S ◽  
Post Translational Modification ◽  
Antioxidant Power

Cardiovascular diseases are associated with oxidative stress and a reduced bioavailability of nitric oxide (NO). To counteract both processes, the administration of S-nitrosoglutathione (GSNO) can be envisaged. GSNO is able to induce protein S-nitrosation (Pr-SNO), which is a post-translational modification of proteins, participating in the storage of NO in tissues, and protect thiol functions from oxidation. However, GSNO antioxidant power is poorly studied, which is probably linked to its low stability. This low stability can be addressed by nanotechnologies that will increase GSNO protection and provide a sustained release of the drug.

scholarly journals Role of the cysteine residues in Arabidopsis thaliana cyclophilin CYP20-3 in peptidyl-prolyl cis–trans isomerase and redox-related functions

2006 ◽  
Vol 401 (1) ◽  
pp. 287-297 ◽  
Author(s):  
Miriam Laxa ◽  
Janine König ◽  
Karl-Josef Dietz ◽  
Andrea Kandlbinder
Keyword(s):  
Conformational Changes ◽  
Protein Function ◽  
Redox Regulation ◽  
Catalytic Efficiency ◽  
Structural Rearrangement ◽  
Disulfide Bridge ◽  
Cysteine Residues ◽  
Active Centre ◽  
Independent Functions

Cyps (cyclophilins) are ubiquitous proteins of the immunophilin superfamily with proposed functions in protein folding, protein degradation, stress response and signal transduction. Conserved cysteine residues further suggest a role in redox regulation. In order to get insight into the conformational change mechanism and functional properties of the chloroplast-located CYP20-3, site-directed mutagenized cysteine→serine variants were generated and analysed for enzymatic and conformational properties under reducing and oxidizing conditions. Compared with the wild-type form, elimination of three out of the four cysteine residues decreased the catalytic efficiency of PPI (peptidyl-prolyl cis–trans isomerase) activity of the reduced CYP20-3, indicating a regulatory role of dithiol–disulfide transitions in protein function. Oxidation was accompanied by conformational changes with a predominant role in the structural rearrangement of the disulfide bridge formed between Cys54 and Cys171. The rather negative Em (midpoint redox potential) of −319 mV places CYP20-3 into the redox hierarchy of the chloroplast, suggesting the activation of CYP20-3 in the light under conditions of limited acceptor availability for photosynthesis as realized under environmental stress. Chloroplast Prx (peroxiredoxins) were identified as interacting partners of CYP20-3 in a DNA-protection assay. A catalytic role in the reduction of 2-Cys PrxA and 2-Cys PrxB was assigned to Cys129 and Cys171. In addition, it was shown that the isomerization and disulfide-reduction activities are two independent functions of CYP20-3 that both are regulated by the redox state of its active centre.

Sign in / Sign up

Export Citation Format

Share Document