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BACKGROUND RESULTS CONCLUSION Advanced glycation end products (AGEs) are compounds formed by non‐enzymatic processes in the Maillard reaction and can cause various chronic diseases. This study explores the AGE formation process in a glucose–amino acid system under both wet‐ and dry‐heating conditions, and analyzes the effect of cysteine in AGE formation.Under wet‐heating conditions, Nε‐carboxymethyllysine (CML) and Nε‐carboxyethyllysine (CEL) concentrations rose for the initial 90 min and subsequently declined after 120 min; after 90 min of heating, the maximum yields in the absence of cysteine were 1151.04 ± 14.01 and 3386.90 ± 26.55 ng mL−1, respectively. The concentration of pyrraline (Pyr) increased after 30 min and then decreased after 60 min with a maximum yield of 777.68 ± 23.36 ng mL−1. However, in dry‐heating models, the AGE concentrations consistently increased with increasing heating time; the maximum yields for CML, CEL and Pyr were 468.66 ± 10.96, 1993.57 ± 14.81 and 1085.74 ± 58.06 ng mL−1, respectively. The addition of cysteine showed an inhibitory effect on AGE formation, especially for Pyr in the dry‐heating model, with inhibition rates ranging from 17.14% to 95.60%.Although wet‐heating models produced more CML and CEL, they produced less Pyr than dry‐heating models. The AGE formation in wet‐heating models positively correlated with the reaction rate; however, the dry‐heating reaction demonstrated a more complex relationship between reaction rate and reaction protocol. Moreover, cysteine exhibited a significant inhibitory effect on AGE production, and the degree of inhibition was proportional to the cysteine concentration. This study provides important insights into the mechanisms for AGE formation under various heating conditions, such as those representing baking (dry‐heating) and steaming conditions (wet‐heating). © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Redox reactions, involving electron transfer, are critical to human physiology. However, progress in understanding redox metabolism is hindered by flawed analytical methods. This review highlights emerging techniques that promise to revolutionize redox research, enhancing our comprehension of human health and disease. Oxygen, vital for aerobic metabolism, also produces reactive oxygen species (ROS), such as superoxide and hydrogen peroxide. While historically seen as harmful, ROS at low concentrations are now recognized as key regulators of cell signaling. A balance between ROS and antioxidants, known as redox balance, is crucial, and deviations can lead to oxidative stress. Recent studies have distinguished beneficial "oxidative eustress" from harmful "oxidative distress." New techniques, such as advanced mass spectrometry and high‐throughput immunoassays, offer improved accuracy in measuring redox states and oxidative damage. These advancements are pivotal for understanding redox signaling, cysteine oxidation, and their implications for disease. Looking ahead, the development of precision redox medicine could lead to better treatments for oxidative stress‐related diseases and foster interventions promoting health. [ABSTRACT FROM AUTHOR]

The quest for novel chromophoric materials with tunable properties to match the natural spectrum of skin tones lacks comprehensive solutions, particularly in harnessing natural proteins for pigment synthesis. This research delved into the synthesis of sub‐micron Keratin‐Cysteine particles inspired by natural pigment production pathways. Adjustment of the initial conditions of the water‐based reaction between keratin, tyrosinase and cysteine, yielded Keratin‐Cysteine particles with colors tunable within the light to intermediate skin tone range. A systematic investigation of the reaction conditions through factorial design of experiment (DOE) identified the sequence of addition of tyrosinase and cysteine as the key determinant of color tone. Ultraviolet‐visible (UV‐Vis) spectroscopy, attenuated total reflectance Fourier transform infrared (ATR‐FTIR) spectroscopy and color analysis were performed to elucidate the reaction mechanism. This research presents a promising approach to chromophore synthesis for cosmetic and biomedical applications. [ABSTRACT FROM AUTHOR]

A novel approach for reducing mercury content in fish meat during post‐packaging storage is developed to extend the margin of their safe consumption. It involves employing a single‐component aqueous medium containing cysteine, as the active agent responsible for displacing mercury from fish proteins and its stabilization in the medium without the need for pH adjustments. The mercury removal efficiency depends on the cysteine concentration and its ratio to fish muscle. Using 1.2 wt% cysteine enables a reduction of mercury in canned Albacore tuna by 25–35%, depending on the fish product type and the exposure time of up to 2 weeks. The potential for the successful application of the developed method in active food packaging solutions is studied for the simultaneous or subsequent purification of the extraction solution through adsorption. Using thiolated silica could potentially enable the extraction process but it is shown that the presence of cysteine significantly hinders the adsorption. [ABSTRACT FROM AUTHOR]

Cysteine is an amino acid present in thiol proteins and often dictates their secondary structures. Although considered nonessential, cysteine may be essential for patients with certain metabolic diseases and can reduce the requirement for dietary methionine. Cysteine and some of its derivatives, such as N‐acetylcysteine, are considered antioxidants and widely used in animal aging studies. To provide insights into the potential anti‐aging effects of cysteine, we systematically reviewed and performed a meta‐analysis to investigate the impact of cysteine supplementation on lifespan using three model organisms: mice, nematodes, and fruit flies. A total of 13 mouse studies, 13 C. elegans studies, and 5 Drosophila studies were included in the analysis. The findings revealed that cysteine supplementation significantly reduced the risk of mortality in mice and C. elegans. Subgroup analysis showed consistent results across different starting times and administration methods and revealed adverse effects of high doses on worms and a lack of effect in nondisease mouse models. Similar to mice, the effects of cysteine supplementation on Drosophila were not statistically significant, except in transgenic flies. The study identified certain limitations, including the quality of the included studies and the potential for publication bias. We also discussed uncertainties in the underlying molecular mechanisms and the clinical application of dietary cysteine. [ABSTRACT FROM AUTHOR]

ABSTRACT Cysteine is the precursor for the biosynthesis of glutathione, a key stress‐protective metabolite, and methionine, which is imperative for cell growth and protein synthesis. The exact mechanism that governs the routing of cysteine toward glutathione or methionine during stresses remains unclear. Our study reveals that under oxidative stress, methionine and glutathione compete for cysteine and that the increased oxidized glutathione (GSSG) levels under stress hinder methionine biosynthesis. Moreover, we find that inhibition occurs as GSSG binds to and accelerates the degradation of cystathionine γ‐synthase, a key enzyme in the methionine synthesis pathway. Consequently, this leads to a reduction in the flux toward methionine‐derived metabolites and redirects cysteine utilization toward glutathione, thereby enhancing plant protection. Our study suggests a novel regulatory feedback loop involving glutathione, methionine, and cysteine, shedding light on the plant stress response and the adaptive rerouting of cysteine. These findings offer new insights into the intricate balance of growth and protection in plants and its impact on their nutritional value due to low methionine levels under stress. [ABSTRACT FROM AUTHOR]

The work presented here investigates whether the TpMesFe+ moiety, which had been previously found to mediate the dioxygenation of cysteine and cysteamine, can do the same with simple thiols, which are not functionalized by an amine group. Accordingly, the complexes TpMesFeSR (R=Ph, iPr) were synthesized and after full characterization exposed to O2. They were found to react unselectively to yield sulfinates, disulfides, and thiosulfones as products. The sulfinate complex TpMesFeO2S‐p‐Tol was prepared independently and found to be air‐stable, suggesting that the additional products are not formed via overoxidation or subsequent reactions of coordinated sulfinate product. To investigate whether the larger reaction space, opened up due to the missing amine donor is responsible, a Tp‐ligand functionalized by a pyridyl donor was employed. A corresponding Tp‐iron(II) chlorido complex was prepared and converted through salt metathesis reactions into the respective thiolate analogues, which were fully characterized and structurally authenticated. However, subsequent O2 reactivity studies did not show an improved selectivity. The reason may lie in a more open reaction pocket in combination with an electronic situation which is less ideal than in case of TpMesFe(cysteamine). [ABSTRACT FROM AUTHOR]

State transitions are an acclimatory response by which plants, algae, and cyanobacteria counteract photosynthetic inefficiency caused by changes in incident light quality. In plants and green algae, state transition 7 (STN7/STT7) kinase promotes state 2 transition. Conserved cysteine residues are implicated in STN7/STT7 regulation, but the precise nature of their involvement remains unclear. Here, an analysis of the STN7 thiols in vitro and a determination of their midpoint redox potential indicate that the lumenal disulfide linkage is unlikely to be redox regulated while the stromal cysteines form a regulatory intramolecular disulfide. We further show that thioredoxin f1 (Trx‐f1) reduces the STN7 stromal disulfide linkage as consistent with a Trx‐f1‐mediated inhibition of the kinase under high light. [ABSTRACT FROM AUTHOR]

Background and Aims: Several studies have highlighted the potent antioxidant properties of N‐acetyl cysteine (NAC). This review aimed to assess the impact of NAC on oxidative stress biomarkers in patients with β‐thalassemia. Methods: The review included articles published before 2024 that investigated the effects of NAC on oxidative stress in individuals with β‐thalassemia. A comprehensive search was conducted across various databases, including Scopus, PubMed, Web of Science, Trip, and CENTRAL. Only English‐language clinical trials were considered for inclusion in this review. Besides, the number needed to treat (NNT) was calculated based on the included studies. Results: Ninety‐nine articles were retrieved from electronic databases, and after a thorough review, eight articles were selected for comprehensive text analysis. The highest dose of NAC administered was 10 mg/kg/day (equivalent to 600 mg/day) over a period of 3–6 months. All the studies assessing the impact of NAC on oxidative stress indicators in β‐thalassemia patients demonstrated positive effects during the 3‐month follow‐up period. Most estimated NNTs fell into 1–5, suggesting significant clinical therapeutic value in this context. Conclusion: The current potency of NAC alone appears to be effective in ameliorating oxidative stress in patients with β‐thalassemia major. While a 3‐month duration seems adequate to demonstrate the antioxidant properties of NAC in this population, larger and well‐designed clinical trials are warranted. Current clinical evidence possesses a high risk of bias. [ABSTRACT FROM AUTHOR]

Hydration reactions consist of the introduction of a molecule of water into a chemical compound and are particularly useful to transform alkynes into carbonyls, which are strategic intermediates in the synthesis of a plethora of compounds. Herein we demonstrate that L–cysteine can catalyse the hydration of activated alkynes in a very effective and fully regioselective manner to access important building blocks in synthetic chemistry such as β‐ketosulfones, amides and esters, in aqueous media. The mild reaction conditions facilitated the integration with enzyme catalysis to access chiral β‐hydroxy sulfones from the corresponding alkynes in a one‐pot cascade process in good yields and excellent enantiomeric ratios. These findings pave the way towards establishing a general method for metal‐free, cost‐effective, and more sustainable alkyne hydration processes. [ABSTRACT FROM AUTHOR]

An imbalance in cysteine (Cys) levels in the cells and plasma has been identified as the risk indicator for various human diseases. The structural similarity of cysteine with its congener homocysteine and glutathione offers challenges in its measurement. Herein, we report a hydrogen‐bonded organic‐inorganic framework of Cu(II) (HOIF) for the selective detection of cysteine over other biothiols. The non‐fluorescent HOIF showed 12‐fold green emission in the presence of cysteine. The monomeric unit of HOIF is stabilized via intermolecular hydrogen bonds, resulting in a non‐porous network structure. Non‐interference from homocysteine, glutathione, and other competitive bio‐analytes revealed explicit affinity of HOIF for cysteine. Fluorimetric titration showed a wide working concentration window (650 nM–800 μM) for measuring cysteine in an aqueous medium. The mechanistic investigation involving HRMS, EPR, and UV‐vis spectroscopic studies revealed the decomplexation of HOIF with Cys, resulting in a fluorescence turn‐on response from the luminescent ligand. Validation using a commercial dye, "Cysteine Green", confirmed the prospect of HOIF for early diagnostic purposes. Utilizing the fluorescence turn‐on property of HOIF in the presence of cysteine, we measured cysteine quantitatively in the blood plasma samples. Bio‐imaging of endogenous cysteine in cancer cells indicated the ability of HOIF to monitor the intracellular cysteine. [ABSTRACT FROM AUTHOR]

A novel, industrially viable synthetic route to (+)‐biotin has been developed starting from L‐cysteine via the known key thiolactone intermediate. The route takes advantage of the in‐built stereochemistry of the cysteine starting material and the best features of the two current industrialized processes. The key transformations are the conversion of L‐cysteine into a hydantoin avoiding racemization followed by catalytic cyanation and thiolactonization to form the required thiolactone intermediate. This known intermediate can be readily further transformed into (+)‐biotin. [ABSTRACT FROM AUTHOR]

The reactivity of Zn2+ tetrahedral complexes with H2O2 was investigated in silico, as a first step in their disruption process. The substrates were chosen to represent the cores of three different zinc finger protein motifs, i. e., a Zn2+ ion coordinated to four cysteines (CCCC), to three cysteines and one histidine (CCCH), and to two cysteines and two histidines (CCHH). The cysteine and histidine ligands were further simplified to methyl thiolate and imidazole, respectively. H2O2 was chosen as an oxidizing agent due to its biological role as a metabolic product and species involved in signaling processes. The mechanism of oxidation of a coordinated cysteinate to sulfenate‐κS and the trends for the different substrates were rationalized through activation strain analysis and energy decomposition analysis in the framework of scalar relativistic Density Functional Theory (DFT) calculations at ZORA‐M06/TZ2P ae // ZORA‐BLYP‐D3(BJ)/TZ2P. CCCC is oxidized most easily, an outcome explained considering both electrostatic and orbital interactions. The isomerization to sulfenate‐κO was attempted to assess whether this step may affect the ligand dissociation; however, it was found to introduce a kinetic barrier without improving the energetics of the dissociation. Lastly, ligand exchange with free thiolates and selenolates was investigated as a trigger for ligand dissociation, possibly leading to metal ejection; molecular docking simulations also support this hypothesis. [ABSTRACT FROM AUTHOR]

The neuronal glycine transporter GlyT2 removes glycine from the synaptic cleft through active Na+, Cl−, and glycine cotransport contributing to the termination of the glycinergic signal as well as supplying substrate to the presynaptic terminal for the maintenance of the neurotransmitter content in synaptic vesicles. Patients with mutations in the human GlyT2 gene (SLC6A5), develop hyperekplexia or startle disease (OMIM 149400), characterized by hypertonia and exaggerated startle responses to trivial stimuli that may have lethal consequences in the neonates as a result of apnea episodes. Post‐translational modifications in cysteine residues of GlyT2 are an aspect of structural interest we analyzed. Our study is compatible with a reversible and short‐lived S‐acylation in spinal cord membranes, detectable by biochemical and proteomics methods (acyl‐Rac binding and IP‐ABE) confirmed with positive and negative controls (palmitoylated and non‐palmitoylated proteins). According to a short‐lived modification, direct labeling using click chemistry was faint but mostly consistent. We have analyzed the physiological properties of a GlyT2 mutant lacking the cysteines with high prediction of palmitoylation and the mutant is less prone to be included in lipid rafts, an effect also observed upon treatment with the palmitoylation inhibitor 2‐bromopalmitate. This work demonstrates there are determinants of lipid raft inclusion associated with the GlyT2 mutated cysteines, which are presumably modified by palmitoylation. [ABSTRACT FROM AUTHOR]

In this work, monodisperse organosilane hybrid polymer microspheres with a particle size of about 5 µm were synthesized using seed swelling polymerization. The organosilicon reagent methacryloxypropyltrimethoxysilane was introduced into the polymer framework as a copolymerization monomer, and the crosslinking degree of the microspheres was improved by the hydrolysis‐condensation reaction of siloxanes. The synthesized hybrid microspheres have good mechanical strength as well as low swelling, with swelling propensity values of 0.167 and 0.348 in methanol and acetonitrile, respectively. Hybrid microspheres modified with cysteine have a hydrophilic interaction chromatography/reversed‐phase liquid chromatography mixed‐mode retention mechanism. Compared to the commercial cysteine‐modified silica column, the synthesized stationary phase has higher separation selectivity for partially acidic or basic samples and better basic resistance for use under high pH mobile phase conditions (at least 10). [ABSTRACT FROM AUTHOR]

BACKGROUND: High moisture meat analog (HMMA) products processed using extrusion have become increasingly popular in the last few years. Because the formation of disulfide bonds is believed to play a critical role in the texturization mechanism, this study aimed to understand how chemical compounds capable of reducing disulfide bonds, specifically cysteine, sodium metabisulfite, and glutathione, affect the texture and the chemical interactions between the proteins. METHOD: Wheat protein blended with cysteine, sodium metabisulfite, or glutathione at levels of 0, 0.5, 1.0, 2.5, 5.0, and 7.5 g kg−1 was extruded at three different temperatures (115, 140, and 165 °C) using a co‐rotating twin‐screw extruder. The feed rate (85 g min−1), the moisture content (600 g kg−1), and the screw speed (300 rpm) were kept constant. Unextruded and extruded material was subjected to sodium dodecyl sulfate‐polyacrylamide gel electrophoresis, polymeric protein fractionation, and sulfhydryl group/disulfide bond analysis. Extruded samples were further analyzed for their hardness and their anisotropic index. RESULTS: The inclusion of reductants significantly affected the structure of the obtained extrudates. Although reducing agents had a relatively small impact on the total amount of disulfide bonds, their action significantly enhanced crosslinking between the proteins. At select conditions, samples with high fibrousness were specifically obtained when cysteine or sodium metabisulfite was included at levels of 5.0 g kg−1. DISCUSSION: In the presence of reducing agents, it is believed that disulfide bonds are split earlier during the process without binding to them, giving the protein strands more time to unravel and align, leading to a better flow behavior and more fibrous products. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Porphyromonas gingivalis is a keystone pathogen in periodontitis, and Streptococcus sanguinis is an abundant oral commensal bacterium associated with periodontal health. However, the interaction between P. gingivalis and S. sanguinis remains obscure. Here, we established a strategy for high‐throughput measurement of the cell number of P. gingivalis in the coculture with S. sanguinis by detecting the concentration of hydrogen sulfate. The interaction between P. gingivalis and over 2000 S. sanguinis single‐gene mutants was characterized using this strategy, and several interaction‐associated genes in S. sanguinis were determined by detecting more P. gingivalis cells in the coculture with matched S. sanguinis mutants. Three S. sanguinis interaction‐associated genes were predicted to be responsible for cysteine metabolism, and the supplementation of exogenous L‐cysteine promoted the cell number of P. gingivalis in the coculture with S. sanguinis. Thus, exogenous L‐cysteine and the compromised cysteine metabolism in S. sanguinis enhanced the growth of P. gingivalis in the existence of S. sanguinis. Additionally, the interaction between P. gingivalis and other Streptococcus spp. was examined, and S. pneumoniae was the only streptococci that had no inhibition on the cell number of P. gingivalis. In total, this study established a new strategy for high‐throughput screening of the interaction between Streptococcus and P. gingivalis and discovered a set of genes in S. sanguinis that impacted the interaction. The influence of exogenous L‐cysteine on the interaction between P. gingivalis and S. sanguinis in the oral cavity needs further investigation. [ABSTRACT FROM AUTHOR]

Chemoselective modification of specific residues within a given protein poses a significant challenge, as the microenvironment of amino acid residues in proteins is variable. Developing a universal molecular platform with tunable chemical warheads can provide powerful tools for precisely labeling specific amino acids in proteins. Cysteine and lysine are hot targets for chemoselective modification, but current cysteine/lysine‐selective warheads face challenges due to cross‐reactivity and unstable reaction products. In this study, a versatile fluorescent platform is developed for highly selective modification of cysteine/lysine under biocompatible conditions. Chloro‐ or phenoxy‐substituted NBSe derivatives effectively labeled cysteine residues in the cellular proteome with high specificity. This finding also led to the development of phenoxy‐NBSe phototheragnostic for the diagnosis and activatable photodynamic therapy of GSH‐overexpressed cancer cells. Conversely, alkoxy‐NBSe derivatives are engineered to selectively react with lysine residues in the cellular environment, exhibiting excellent anti‐interfering ability against thiols. Leveraging a proximity‐driven approach, alkoxy‐NBSe probes are successfully designed to demonstrate their utility in bioimaging of lysine deacetylase activity. This study also achieves integrating a small photosensitizer into lysine residues of proteins in a regioselective manner, achieving photoablation of cancer cells activated by overexpressed proteins. [ABSTRACT FROM AUTHOR]

Background and Purpose: The analgesic action of paracetamol involves KV7 channels, and its metabolite N‐acetyl‐p‐benzo quinone imine (NAPQI), a cysteine modifying reagent, was shown to increase currents through such channels in nociceptors. Modification of cysteine residues by N‐ethylmaleimide, H2O2, or nitric oxide has been found to modulate currents through KV7 channels. The study aims to identify whether, and if so which, cysteine residues in neuronal KV7 channels might be responsible for the effects of NAPQI. Experimental Approach: To address this question, we used a combination of perforated patch‐clamp recordings, site‐directed mutagenesis, and mass spectrometry applied to recombinant KV7.1 to KV7.5 channels. Key Results: Currents through the cardiac subtype KV7.1 were reduced by NAPQI. Currents through all other subtypes were increased, either by an isolated shift of the channel voltage dependence to more negative values (KV7.3) or by such a shift combined with increased maximal current levels (KV7.2, KV7.4, KV7.5). A stretch of three cysteine residues in the S2‐S3 linker region of KV7.2 was necessary and sufficient to mediate these effects. Conclusion and Implication: The paracetamol metabolite N‐acetyl‐p‐benzo quinone imine (NAPQI) modifies cysteine residues of KV7 subunits and reinforces channel gating in homomeric and heteromeric KV7.2 to KV7.5, but not in KV7.1 channels. In KV7.2, a triple cysteine motif located within the S2‐S3 linker region mediates this reinforcement that can be expected to reduce the excitability of nociceptors and to mediate antinociceptive actions of paracetamol. [ABSTRACT FROM AUTHOR]

Cysteine thiols are susceptible to various oxidative posttranslational modifications (PTMs) due to their high chemical reactivity. Thiol‐based PTMs play a crucial role in regulating protein functions and are key contributors to cellular redox signaling. Although reversible thiol‐based PTMs, such as disulfide bond formation, S‐nitrosylation, and S‐glutathionylation, have been extensively studied for their roles in redox regulation, thiol sulfinic acid (–SO2H) modification is often perceived as irreversible and of marginal significance in redox signaling. Here, we revisit this narrow perspective and shed light on the redox regulatory roles of –SO2H in plant stress signaling. We provide an overview of protein sulfinylation in plants, delving into the roles of hydrogen peroxide‐mediated and plant cysteine oxidase‐catalyzed formation of –SO2H, highlighting the involvement of –SO2H in specific regulatory signaling pathways. Additionally, we compile the existing knowledge of the –SO2H reducing enzyme, sulfiredoxin, offering insights into its molecular mechanisms and biological relevance. We further summarize current proteomic techniques for detecting –SO2H and furnish a list of experimentally validated cysteine –SO2H sites across various species, discussing their functional consequences. This review aims to spark new insights and discussions that lead to further investigations into the functional significance of protein –SO2H‐based redox signaling in plants. Summary statement: This review expands upon the conventional understanding of cysteine thiol sulfinic acid modification and provides an updated overview of its redox‐dependent regulatory functions in the context of plant stress signaling pathways. [ABSTRACT FROM AUTHOR]

Modern society's keen regard for aesthetics made hair products an integral part of a multi‐billion‐dollar cosmetic industry. Hair care products (e.g., shampoos and conditioners) and chemical treatments (e.g., bleaching and permanent waving) result in various effects on the morphological attributes of hair. Generally, water adsorbed on the hair surface is known to significantly dictate the hair's mechanical characteristics (smoothness and friction), and hair's macroscopic wettability has been commonly used to indicate its surface properties. However, an approach to selectively characterize the hydration water in the hair surface is required to accurately understand the intermolecular events between the hair and its vicinal water. In this paper, we successfully obtained the infrared (IR) absorption spectra of the hydration water of human hair. We employed the multivariate curve resolution‐alternating least square (MCR‐ALS) method to separate the hydration and bulk water spectra from the whole spectra. Comparing the IR spectra of the hydration water of chemically untreated and bleached hair samples, we conclude that water molecules form strong hydrogen bonds with the bleached hair surface due to the destruction of the hair's hydrophobic outer layer and the consequent formation of hydrophilic residues. [ABSTRACT FROM AUTHOR]

A facilely prepared composite based on Polyvinyl alcohol anchored‐ L‐cysteine (PVA‐L‐CYS) demonstrated efficient functionality in the elimination of heavy metals (Hg, Cr, Pb, and Cd) from working wastewater. The synthesis of the composite was validated through a comprehensive characterization utilizing various analytical techniques to ensure the composite's structural, chemical, and physical properties. At ambient temperature, pH of 4–5.5, interaction time of 15–20 minutes, and concentration of 200 mg/L metal ions, the composite exhibited a maximum retention capacity of 48.5, 25, 45.25, and 44.25 mg/g for Hg, Cr, Pb, and Cd, respectively. Langmuir modeling was establish to be more fitting to the practical results than Freundlich, providing theoretical values of 49.02, 25.97, 46.08, and 44.84 mg/g for Hg, Cr, Pb, and Cd, respectively. The kinetics of PVA‐L‐CYS composite was accurately predicted by model of the pseudo‐first‐order kinetic. Thermodynamic prospects indicated a spontaneous, exothermic, and favorable uptake process at low temperatures. Efficient elution of the heavy metal ions from the overloaded composite was performed using 1 M HNO3. In accordance with WHO and FAO guidelines, the successful elimination of working metal ions from wastewater utilizing the PVA‐L‐CYS composite was demonstrated in a single cycle before discharge into the marine environment. [ABSTRACT FROM AUTHOR]

An advanced insulin synthesis is presented that utilizes one‐pot/stepwise disulfide bond formation enabled by acid‐activated S‐protected cysteine sulfoxides in the presence of chloride anion. S‐chlorocysteine generated from cysteine sulfoxides reacts with an S‐protected cysteine to afford S‐sulfenylsulfonium cation, which then furnishes the disulfide or reversely returns to the starting materials depending on the S‐protection employed and the reaction conditions. Use of S‐acetamidomethyl cysteine (Cys(Acm)) and its sulfoxide (Cys(Acm)(O)) selectively give the disulfide under weak acid conditions in the presence of MgCl2 even if S‐p‐methoxybenzyl cysteine (Cys(MBzl)) and its sulfoxide (Cys(MBzl)(O)) are also present. In contrast, the S‐MBzl pair yields the disulfide under more acidic conditions in the presence of a chloride anion source. These reaction conditions allowed a one‐pot insulin synthesis. Additionally, lipidated insulin was prepared by a one‐pot disulfide‐bonding/lipidation sequence. [ABSTRACT FROM AUTHOR]

The knowledge regarding the origins of life from inanimate materials is still elusive. It was proposed that biological building blocks evolved from the inorganic substances present in the early earth conditions. However, the process by which chemistry can be converted into biology has not yet been achieved in the laboratory. The artificial system in the out‐of‐equilibrium state must maintain a few critical features of life, like compartmentalization, metabolism, and replication, to be considered alive. In this direction, working with cysteine (Cys)‐based molecules is strategic to understand the life evolution process. The presence of the sulphydryl (−SH) group in the Cys‐residue can build a dynamic equilibrium state through disulfide redox chemistry under the proper guidance of oxidizing and reducing agents. In this review article, our primary focus is to discuss the Cys‐containing short‐peptide‐based self‐assembly and disassembly processes. The formation of disulfide bonds sometimes helps in the self‐assembly process and gelation, but the reverse is also true in some cases. In the later part of this article, we cover the fact that these sulphydryl‐based systems have shown their adaptability to mimic different life‐essential criteria to participate in Darwinian evolution. [ABSTRACT FROM AUTHOR]

Infectious diseases have been jeopardized problem that threaten public health over a long period of time. The growing prevalence of drug‐resistant pathogens and infectious cases have led to a decrease in the number of effective antibiotics, which highlights the urgent need for the development of new antibacterial agents. Serine acetyltransferase (SAT), also known as CysE in certain bacterial species, and O‐acetylserine sulfhydrylase (OASS), also known as CysK in select bacteria, are indispensable enzymes within the cysteine biosynthesis pathway of various pathogenic microorganisms. These enzymes play a crucial role in the survival of these pathogens, making SAT and OASS promising targets for the development of novel anti‐infective agents. In this comprehensive review, we present an introduction to the structure and function of SAT and OASS, along with an overview of existing inhibitors for SAT and OASS as potential antibacterial agents. Our primary focus is on elucidating the inhibitory activities, structure–activity relationships, and mechanisms of action of these inhibitors. Through this exploration, we aim to provide insights into promising strategies and prospects in the development of antibacterial agents that target these essential enzymes. [ABSTRACT FROM AUTHOR]

It has remained unknown how cells reduce cystine taken up from the extracellular space, which is a required step for further utilization of cysteine in key processes such as protein or glutathione synthesis. Here, we show that the thioredoxin-related protein of 14 kDa (TRP14, encoded by TXNDC17) is the rate-limiting enzyme for intracellular cystine reduction. When TRP14 is genetically knocked out, cysteine synthesis through the transsulfuration pathway becomes the major source of cysteine in human cells, and knockout of both pathways becomes lethal in C. elegans subjected to proteotoxic stress. TRP14 can also reduce cysteinyl moieties on proteins, rescuing their activities as here shown with cysteinylated peroxiredoxin 2. Txndc17 knockout mice were, surprisingly, protected in an acute pancreatitis model, concomitant with activation of Nrf2-driven antioxidant pathways and upregulation of transsulfuration. We conclude that TRP14 is the evolutionarily conserved enzyme principally responsible for intracellular cystine reduction in C. elegans, mice, and humans. Synopsis: Metabolic utilization of cysteine requires reduction of cystine taken up from extracellular sources. Here, TXNDC17 -encoded TRP14 is identified as the main enzyme catalyzing this step, regulating protein cysteinylation and cysteine homeostasis in concert with the transsulfuration pathway. Thioredoxin-related protein TRP14 is the rate-limiting enzyme in mammalian cytosolic cystine reduction. Genetic ablation of TRP14 redirects cysteine biosynthesis towards the transsulfuration pathway as alternative, methionine-based source of cysteine. TRP14 also reduces cysteinylated proteins and potentially modulates protein function, such as reactivation of cysteinylated peroxiredoxin 2 through its decysteinylation. Txndc17 -deficient mice are protected from acute pancreatitis pathophysiology through activation of Nrf2-mediated antioxidant pathways and primed upregulation of transsulfuration. Interplay between TRP14 and transsulfuration in cysteine metabolism appears conserved across species, as knockout of both pathways becomes lethal in C. elegans subjected to proteotoxic stress. A thioredoxin-related protein controls cysteine homeostasis in parallel to the transsulfuration pathway, and can also modulate protein function via protein decysteinylation. [ABSTRACT FROM AUTHOR]

In spite of 150 years of studying malaria, the unique features of the malarial parasite, Plasmodium, still perplex researchers. One of the methods by which the parasite manages its gene expression is epigenetic regulation, the champion of which is PfGCN5, an essential enzyme responsible for acetylating histone proteins. PfGCN5 is a ∼170 kDa chromatin‐remodeling enzyme that harbors the conserved bromodomain and acetyltransferase domain situated in its C‐terminus domain. Although the PfGCN5 proteolytic processing is essential for its activity, the specific protease involved in this process still remains elusive. Identification of PfGCN5 interacting proteins through immunoprecipitation (IP) followed by LC‐tandem mass spectrometry analysis revealed the presence of food vacuolar proteins, such as the cysteine protease Falcipain 3 (FP3), in addition to the typical members of the PfGCN5 complex. The direct interaction between FP3 and PfGCN5 was further validated by in vitro pull‐down assay as well as IP assay. Subsequently, use of cysteine protease inhibitor E64d led to the inhibition of protease‐specific processing of PfGCN5 with concomitant enrichment and co‐localization of PfGCN5 and FP3 around the food vacuole as evidenced by confocal microscopy as well as electron microscopy. Remarkably, the proteolytic cleavage of the nuclear protein PfGCN5 by food vacuolar protease FP3 is exceptional and atypical in eukaryotic organisms. Targeting the proteolytic processing of GCN5 and the associated protease FP3 could provide a novel approach for drug development aimed at addressing the growing resistance of parasites to current antimalarial drugs. [ABSTRACT FROM AUTHOR]

Aqueous soft matter, including supramolecular hydrogels capable of exhibiting stimuli–responsive macroscopic phase transitions, has attracted increasing attention for the exploration of functional soft materials. However, the investigation of supramolecular hydrogels that undergo autonomous and multiple macroscopic phase transitions (e.g., gel–sol–gel, sol–gel–sol) in response to the surrounding environment without repeated additions of stimuli has remained largely unexplored. In this study, the oxidation‐responsive autonomous gel–sol–gel transitions of supramolecular hydrogels fabricated via the self‐assembly of a simple fluorenylmethyloxycarbonyl (Fmoc)‐protected, benzylated cysteine (Fmoc‐CBzl) is presented. During the evaluation of the oxidation process of Fmoc‐CBzl, it is revealed that the oxidized products, two diastereomeric sulfoxides (Fmoc‐CBzl‐(R)‐O and Fmoc‐CBzl‐(S)‐O), exhibit significantly different self‐assembly propensities under aqueous conditions. It may be noteworthy that the chirality of sulfoxide is largely overlooked and not effectively used to modulate supramolecular, self‐assembled nanostructures. The difference in the self‐assembly propensities and kinetics of self‐assembly/disassembly as well as co‐assembly will contribute to oxidation‐responsive autonomous gel–sol–gel transitions. [ABSTRACT FROM AUTHOR]

Peptide and protein postmodification have gained significant attention due to their extensive impact on biomolecule engineering and drug discovery, of which cysteine‐specific modification strategies are prominent due to their inherent nucleophilicity and low abundance. Herein, the study introduces a novel approach utilizing multifunctional 5‐substituted 1,2,3‐triazine derivatives to achieve multifaceted bioconjugation targeting cysteine‐containing peptides and proteins. On the one hand, this represents an inaugural instance of employing 1,2,3‐triazine in biomolecular‐specific modification within a physiological solution. On the other hand, as a powerful combination of precision modification and biorthogonality, this strategy allows for the one‐pot dual‐orthogonal functionalization of biomolecules utilizing the aldehyde group generated simultaneously. 1,2,3‐Triazine derivatives with diverse functional groups allow conjugation to peptides or proteins, while bi‐triazines enable peptide cyclization and dimerization. The examination of the stability of bi‐triazines revealed their potential for reversible peptide modification. This work establishes a comprehensive platform for identifying cysteine‐selective modifications, providing new avenues for peptide‐based drug development, protein bioconjugation, and chemical biology research. [ABSTRACT FROM AUTHOR]

Short peptide sequences consisting of two cysteine residues separated by three other amino acids display complete change from random coil to α‐helical secondary structure in response to addition of Ag+ ions. The folded CXXXC/Ag+ complex involves formation of multinuclear Ag+ species and is stable in a wide pH range from below 3 to above 8. The complex is stable through reversed‐phase HPLC separation as well as towards a physiological level of chloride ions, based on far‐UV circular dichroism spectroscopy. In electrospray MS under acidic conditions a peptide dimer with four Ag+ ions bound was observed, and modelling based on potentiometric experiments supported this to be the dominating complex at neutral pH together with a peptide dimer with 3 Ag+ and one proton at lower pH. The complex was demonstrated to work as a N‐terminal nucleation site for inducing α‐helicity into longer peptides. This type of silver‐mediated peptide assembly and folding may be of more general use for stabilizing not only peptide folding but also for controlling oligomerization even under acidic conditions. [ABSTRACT FROM AUTHOR]

The carboxyl‐terminal (C‐terminal) S‐[(Z)‐2‐aminovinyl]‐cysteine (AviCys) analogs have been identified in four families of ribosomally synthesized and post‐translationally modified peptides (RiPPs): lanthipeptides, linaridins, thioamitides, and lipolanthines. Within identified biosynthetic pathways, a highly reactive enethiol intermediate, formed through an oxidative decarboxylation catalyzed by a LanD‐like flavoprotein, can undergo two types of cyclization: a Michael addition with a dehydroamino acid or a coupling reaction initiated by a radical species. The collaborative actions of LanD‐like proteins with diverse enzymes involved in dehydration, dethiolation or cyclization lead to the construction of structurally distinct peptide natural products with analogous C‐terminal macrocyclic moieties. This concept summarizes existing knowledge regarding biosynthetic pathways of AviCys analogs to emphasize the diversity of biosynthetic mechanisms that paves the way for future genome mining explorations into diverse peptide natural products. [ABSTRACT FROM AUTHOR]

Zinc anodes in aqueous batteries face challenges such as dendrite growth and interfacial instability. This study investigates the use of cysteine as an electrolyte additive to address these issues. By establishing the correlation between the size of zinc nuclei and the surface tensions/contact angle at the electrolyte‐anode interface, it is demonstrated that the addition of cysteine in the electrolyte alters the surface tensions/contact angle at the electrolyte‐anode interface and the nucleation process of zinc. This alteration results in the formation of smaller and more dispersed nuclei, as opposed to the formation of larger island grains. This has a profound impact on the subsequent deposition growth process, enabling smooth and uniform zinc electrodeposition without the formation of dendrites. Additionally, cysteine molecules create a stable interface during zinc plating and stripping, effectively preventing corrosion from side reactions. The incorporation of cysteine in the electrolyte significantly enhances cycling stability and extends the lifespan of zinc anodes in aqueous batteries. [ABSTRACT FROM AUTHOR]

Soybean meal is the main protein source for animal feed, but it has low content of the essential amino acids cysteine (Cys) and methionine (Met). In this research, an exotic germplasm (PI 399000) was crossed with 'Woodruff' to develop an F5‐derived recombinant inbred line (RIL) population for mapping quantitative trait loci for seed composition. The population was grown in six environments, and protein, oil, Cys, and Met were determined with near‐infrared spectroscopy. RILs were genotyped with the SoySNP6K BeadChip, and 1865 SNPs were used for analysis. QTL analysis identified three loci on chromosomes (Chrs) 6, 15 and 17 in at least five environments for protein; two QTLs on Chrs 14 and 17 in all environments for oil; three QTLs on Chrs 3, 6 and 10 for Cys and Met in at least three environments; and two QTLs for seed size on Chrs 17 and 20 in all environments. Stacking of protein and Cys + Met QTLs can increase both traits simultaneously, and 13 breeding lines were identified with improved seed composition. The markers linked to the QTLs can be used to assist the development of cultivars with improved meal quality. [ABSTRACT FROM AUTHOR]

SUMMARY: Glutathione (GSH) is required for various physiological processes in plants, including redox regulation and detoxification of harmful compounds. GSH also functions as a repository for assimilated sulfur and is actively catabolized in plants. In Arabidopsis, GSH is mainly degraded initially by cytosolic enzymes, γ‐glutamyl cyclotransferase, and γ‐glutamyl peptidase, which release cysteinylglycine (Cys‐Gly). However, the subsequent enzyme responsible for catabolizing this dipeptide has not been identified to date. In the present study, we identified At4g17830 as a Cys‐Gly dipeptidase, namely cysteinylglycine peptidase 1 (CGP1). CGP1 complemented the phenotype of the yeast mutant that cannot degrade Cys‐Gly. The Arabidopsis cgp1 mutant had lower Cys‐Gly degradation activity than the wild type and showed perturbed concentrations of thiol compounds. Recombinant CGP1 showed reasonable Cys‐Gly degradation activity in vitro. Metabolomic analysis revealed that cgp1 exhibited signs of severe sulfur deficiency, such as elevated accumulation of O‐acetylserine (OAS) and the decrease in sulfur‐containing metabolites. Morphological changes observed in cgp1, including longer primary roots of germinating seeds, were also likely associated with sulfur starvation. Notably, At4g17830 has previously been reported to encode an N2‐acetylornithine deacetylase (NAOD) that functions in the ornithine biosynthesis. The cgp1 mutant did not show a decrease in ornithine content, whereas the analysis of CGP1 structure did not rule out the possibility that CGP1 has Cys‐Gly dipeptidase and NAOD activities. Therefore, we propose that CGP1 is a Cys‐Gly dipeptidase that functions in the cytosolic GSH degradation pathway and may play dual roles in GSH and ornithine metabolism. Significance Statement: In this study, we identified At4g17830 (CGP1) as a Cys‐Gly dipeptidase that functions in the glutathione (GSH) degradation pathway and revealed its importance in plant metabolism and growth, especially under sulfur starvation. Notably, CGP1 has been reported as an N2‐acetylornithine deacetylase (NAOD) that participates in the ornithine biosynthesis pathway; therefore, our findings imply that CGP1 is a bifunctional enzyme that plays vital roles in both sulfur and nitrogen metabolism. [ABSTRACT FROM AUTHOR]

SUMMARY: Meloidogyne incognita is one of the most widely distributed plant‐parasitic nematodes and causes severe economic losses annually. The parasite produces effector proteins that play essential roles in successful parasitism. Here, we identified one such effector named MiCE108, which is exclusively expressed within the nematode subventral esophageal gland cells and is upregulated in the early parasitic stage of M. incognita. A yeast signal sequence trap assay showed that MiCE108 contains a functional signal peptide for secretion. Virus‐induced gene silencing of MiCE108 impaired the parasitism of M. incognita in Nicotiana benthamiana. The ectopic expression of MiCE108 in Arabidopsis suppressed the deposition of callose, the generation of reactive oxygen species, and the expression of marker genes for bacterial flagellin epitope flg22‐triggered immunity, resulting in increased susceptibility to M. incognita, Botrytis cinerea, and Pseudomonas syringae pv. tomato (Pst) DC3000. The MiCE108 protein physically associates with the plant defense protease RD21A and promotes its degradation via the endosomal‐dependent pathway, or 26S proteasome. Consistent with this, knockout of RD21A compromises the innate immunity of Arabidopsis and increases its susceptibility to a broad range of pathogens, including M. incognita, strongly indicating a role in defense against this nematode. Together, our data suggest that M. incognita deploys the effector MiCE108 to target Arabidopsis cysteine protease RD21A and affect its stability, thereby suppressing plant innate immunity and facilitating parasitism. [ABSTRACT FROM AUTHOR]

Neuroinflammation is an underlying feature of neurodegenerative conditions, often appearing early in the aetiology of a disease. Microglial activation, a prominent initiator of neuroinflammation, can be induced through lipopolysaccharide (LPS) treatment resulting in expression of the inducible form of nitric oxide synthase (iNOS), which produces nitric oxide (NO). NO post‐translationally modifies cysteine thiols through S‐nitrosylation, which can alter function of the target protein. Furthermore, packaging of these NO‐modified proteins into extracellular vesicles (EVs) allows for the exertion of NO signalling in distant locations, resulting in further propagation of the neuroinflammatory phenotype. Despite this, the NO‐modified proteome of activated microglial EVs has not been investigated. This study aimed to identify the protein post‐translational modifications NO signalling induces in neuroinflammation. EVs isolated from LPS‐treated microglia underwent mass spectral surface imaging using time of flight‐secondary ion mass spectrometry (ToF‐SIMS), in addition to iodolabelling and comparative proteomic analysis to identify post‐translation S‐nitrosylation modifications. ToF‐SIMS imaging successfully identified cysteine thiol side chains modified through NO signalling in the LPS treated microglial‐derived EV proteins. In addition, the iodolabelling proteomic analysis revealed that the EVs from LPS‐treated microglia carried S‐nitrosylated proteins indicative of neuroinflammation. These included known NO‐modified proteins and those associated with LPS‐induced microglial activation that may play an essential role in neuroinflammatory communication. Together, these results show activated microglia can exert broad NO signalling changes through the selective packaging of EVs during neuroinflammation. [ABSTRACT FROM AUTHOR]

As a biothiol, cysteine (Cys) is essential to both physiological and pathological processes and has been associated with many diseases, including neurological disorders, rheumatoid arthritis, and renal dysfunction. Therefore, the development of a high‐performance probe for detecting Cys levels can help prevent and diagnose disease. In this study, a ratiometric fluorescent probe based on a novel fluorophore was developed for detecting Cys, and it showed high specificity and a rapid response time toward Cys. This probe demonstrates excellent biocompatibility and has been utilized effectively for the imaging of Cys in living cells. [ABSTRACT FROM AUTHOR]

SUMMARY: Alcohol dehydrogenases (ADHs) are a group of zinc‐binding enzymes belonging to the medium‐length dehydrogenase/reductase (MDR) protein superfamily. In plants, these enzymes fulfill important functions involving the reduction of toxic aldehydes to the corresponding alcohols (as well as catalyzing the reverse reaction, i.e., alcohol oxidation; ADH1) and the reduction of nitrosoglutathione (GSNO; ADH2/GSNOR). We investigated and compared the structural and biochemical properties of ADH1 and GSNOR from Arabidopsis thaliana. We expressed and purified ADH1 and GSNOR and determined two new structures, NADH‐ADH1 and apo‐GSNOR, thus completing the structural landscape of Arabidopsis ADHs in both apo‐ and holo‐forms. A structural comparison of these Arabidopsis ADHs revealed a high sequence conservation (59% identity) and a similar fold. In contrast, a striking dissimilarity was observed in the catalytic cavity supporting substrate specificity and accommodation. Consistently, ADH1 and GSNOR showed strict specificity for their substrates (ethanol and GSNO, respectively), although both enzymes had the ability to oxidize long‐chain alcohols, with ADH1 performing better than GSNOR. Both enzymes contain a high number of cysteines (12 and 15 out of 379 residues for ADH1 and GSNOR, respectively) and showed a significant and similar responsivity to thiol‐oxidizing agents, indicating that redox modifications may constitute a mechanism for controlling enzyme activity under both optimal growth and stress conditions. [ABSTRACT FROM AUTHOR]

Solvents influence the structure, aggregation and folding behaviors of solvatochromic compounds. Ultrasensitive solvent mediated chiroptical response is conducive to the fabrication of molecular platform for sensing and recognition, which however, remains great challenges in conceptual or applicable design. Here we report a cysteine‐based single benzene chromophore system that shows ultrasensitivity to solvents. Compared to the ratiometrically responsive systems, the chiroptical activities could be triggered or inverted depending on the substituents of chiral entities with an ultralow solvent volume fraction (<1 vol %). One drop of dipolar solvents shall significantly induce the emergence or inversion of chiroptical signals in bulky phases. Based on the experimental and computational studies, the ultrasensitivity is contributed to the intimate interplay between solvents and chiral compounds that anchors the specific chiral conformation. It illustrates that structurally simple organic compounds without aggregation or folding behaviors possess pronounced solvatochiroptical properties, which sheds light on the next‐generation of chiroptical sensors and switches. [ABSTRACT FROM AUTHOR]

Malate dehydrogenases (MDHs) catalyze a reversible NAD(P)‐dependent‐oxidoreductase reaction that plays an important role in central metabolism and redox homeostasis of plant cells. Recent studies suggest a moonlighting function of plastidial NAD‐dependent MDH (plNAD‐MDH; EC 1.1.1.37) in plastid biogenesis, independent of its enzyme activity. In this study, redox effects on activity and conformation of recombinant plNAD‐MDH from Arabidopsis thaliana were investigated. We show that reduced plNAD‐MDH is active while it is inhibited upon oxidation. Interestingly, the presence of its cofactors NAD+ and NADH could prevent oxidative inhibition of plNAD‐MDH. In addition, a conformational change upon oxidation could be observed via non‐reducing SDS‐PAGE. Both effects, its inhibition and conformational change, were reversible by re‐reduction. Further investigation of single cysteine substitutions and mass spectrometry revealed that oxidation of plNAD‐MDH leads to oxidation of all four cysteine residues. However, cysteine oxidation of C129 leads to inhibition of plNAD‐MDH activity and oxidation of C147 induces its conformational change. In contrast, oxidation of C190 and C333 does not affect plNAD‐MDH activity or structure. Our results demonstrate that plNAD‐MDH activity can be reversibly inhibited, but not inactivated, by cysteine oxidation and might be co‐regulated by the availability of its cofactors in vivo. [ABSTRACT FROM AUTHOR]

Alternative splicing (AS) is an important regulatory mode at the post‐transcriptional level, through which many flowering genes regulate floral transition by producing multiple transcripts, and splicing factors have essential roles in this process. Hydrogen sulphide (H2S) is a newly found gasotransmitter that has critical physiological roles in plants, and one of its potential modes of action is via persulfidation of target proteins at specific cysteine sites. Previously, it has been shown that both the splicing factor AtU2AF65a and H2S are involved in the regulation of plant flowering. This study found that, in Arabidopsis, the promoting effect of H2S on flowering was abolished in atu2af65a‐4 mutants. Transcriptome analyses showed that when AtU2AF65a contained mutations, the regulatory function of H2S during the AS of many flowering genes (including SPA1, LUH, LUG and MAF3) was inhibited. The persulfidation assay showed that AtU2AF65a can be persulfidated by H2S, and the RNA immunoprecipitation data indicated that H2S could alter the binding affinity of AtU2AF65a to the precursor messenger RNA of the above‐mentioned flowering genes. Overall, our results suggest that H2S may regulate the AS of flowering‐related genes through persulfidation of splicing factor AtU2AF65a and thus lead to early flowering in plants. Summary statement: This study describes a novel pathway through which hydrogen sulphide promotes the flowering of Arabidopsis via persulfidation of the splicing factor, AtU2AF65a. AtU2AF65a persulfidation changes the alternative splicing patterns of several downstream flowering genes, ultimately affecting the flowering time of Arabidopsis. [ABSTRACT FROM AUTHOR]

A biocompatible fluorescence sensor for cysteine detection receives wide appreciation recently, because of its importance in the medical field. Functionalized graphene quantum dots (GQDs) are recently emerging biocompatible quantum dots, which are considered as suitable candidates for biomolecule detection. Motivated by this concept, here we have developed a versatile fluorescent probe based on 3‐aminocoumarin (AMC) functionalized GQDs for the detection of cysteine (Cys). Modification on GQD with AMC resulted in a stable fluorescent probe with an enhancement in quantum yield of about 84% and 40 nm redshift in emission peak compared with bare GQD. The modified GQD is then used for the sensitive and selective detection of cysteine in aqueous media. The detection of Cys within the linear range of 50 nM to 1.5 μM was achieved with a detection limit (LOD) of 0.86 nM. Here, the AMC‐GQD exhibit a turn‐off fluorescence sensing behavior. The quenching mechanism was also explored. The sensing process follows dynamic quenching mechanism, which is attributed to the photoinduced charge transfer from AMC‐GQD to Cys. The Stern–Volmer plot, energy‐level alignment obtained from cyclic voltammetry measurements and density functional theory predictions give a valid proof for this. Furthermore, the sensor was applied efficiently to the determination of Cys in real water samples. [ABSTRACT FROM AUTHOR]

L‐3,4‐dihydroxyphenylalanine (levodopa or L–DOPA) a precursor of neurotransmitter dopamine, has been universally prescribed as a gold standard for treatment of Parkinson's Disease (PD). However, direct administration of L–DOPA has risky adverse effects which makes it challenging in the treatment of PD. Hence developing simple detection platform for sensing of L–DOPA is significant. In this work, we have developed cysteine stabilized copper nanocluster quenched with Fe2+ (Fe2+@cys@CuNC) and used as both fluorescent and colorimetric probe for detection of L–DOPA. L–DOPA attributed a fluorescence quenching effect on developed probe. Fe2+@cys@CuNC detected L–DOPA within a linear range from 0.06 mM to 1.31 mM with a low limit of detection (LoD) of 6.57 nM. The probe also exhibited high selectivity for L–DOPA over other biomolecules and neurotransmitters. Furthermore, the capability of this probe was validated by sensing L–DOPA from human serum with excellent recovery rates of 85.75 % to 115.07 %. A low‐cost paper strip‐based portable detection platform was also developed for visual detection of L–DOPA. [ABSTRACT FROM AUTHOR]

In this study we develop a strategy to insulate 6,6 ‐Phenyl C61 butyric acid methyl ester (PCBM) on the basal plane of transition metal dichalcogenides (TMDs). Concretely single layers of MoS2, MoSe2, MoTe2, WS2, WSe2 and WTe2 and ultrathin MoO2 and WO2 were grown via chemical vapor deposition (CVD). Then, the thiol group of a PCBM modified with cysteine reacts with the chalcogen vacancies on the basal plane of TMDs, yielding PCBM‐MoS2, PCBM‐MoSe2, PCBM‐WS2, PCBM‐WSe2, PCBM‐WTe2, PCBM‐MoO2 and PCBM‐WO2. Afterwards, all the hybrid materials were characterized using several techniques, including XPS, Raman spectroscopy, TEM, AFM, and cyclic voltammetry. Furthermore, PCBM causes a unique optical and electrical impact in every TMDs. For MoS2 devices, the conductivity and photoluminescence (PL) emission achieve a remarkable enhancement of 1700 % and 200 % in PCBM‐MoS2 hybrids. Similarly, PCBM‐MoTe2 hybrids exhibit a 2‐fold enhancement in PL emission at 1.1 eV. On the other hand, PCBM‐MoSe2, PCBM‐WSe2 and PCBM‐WS2 hybrids exhibited a new interlayer exciton at 1.29–1.44, 1.7 and 1.37‐154 eV along with an enhancement of the photo‐response by 2400, 3200 and 600 %, respectively. Additionally, PCBM‐WTe2 and PCBM‐WO2 showed a modest photo‐response, in sharp contrast with pristine WTe2 or WO2 which archive pure metallic character. [ABSTRACT FROM AUTHOR]

This article discusses the use of microenvironment-differential imaging to identify regional preferences for ferroptosis, a type of cell regulation that has potential applications in cancer treatment. The authors propose a protocol for regulating ferroptosis based on region monitoring, differentiation analysis, and chemical intervention. They also describe the development of a path-independent equifinal fluorescence probe that can enhance the contrast between different microenvironments and metabolites. The results of their experiments suggest that ferroptosis prefers microenvironments with low demethylated metabolites of methionine, such as reoxygenation or oxidative stress. This research contributes to the development of precision treatment methods. [Extracted from the article]

Reduction of the 17,18‐double bond in the D‐ring during chlorophyll biosynthesis is catalyzed by the rare, naturally occurring photoenzyme protochlorophyllide oxidoreductase (POR). A conserved tyrosine residue has been suggested to donate a proton to C18 of the substrate in the past decades. Taylor and colleagues scrutinized the model with a powerful tool that utilized a modified genetic code to introduce fluorinated tyrosine analogues into POR. The presented results show that the suggested catalytically critical tyrosine is unlikely to participate in the reaction chemistry but is required for substrate binding, and instead, a cysteine residue preceding the lid helix is proposed to have the role of proton donor. [ABSTRACT FROM AUTHOR]

Acute promyelocytic leukemia (APL) is characterized by the fusion gene promyelocytic leukemia–retinoic acid receptor‐alpha (PML–RARA) and is conventionally treated with arsenic trioxide (ATO). ATO binds directly to the RING finger, B‐box, coiled‐coil (RBCC) domain of PML and initiates degradation of the fusion oncoprotein PML–RARA. However, the mutational hotspot at C212–S220 disrupts ATO binding, leading to drug resistance in APL. Therefore, structural consequences of these point mutations in PML that remain uncertain require comprehensive analysis. In this study, we investigated the structure‐based ensemble properties of the promyelocytic leukemia‐RING‐B‐box‐coiled‐coil (PML‐RBCC) domains and ATO‐resistant mutations. Oligomeric studies reveal that PML‐RBCC wild‐type and mutants C212R, S214L, A216T, L217F, and S220G predominantly form tetramers, whereas mutants C213R, A216V, L218P, and D219H tend to form dimers. The stability of the dimeric mutants was lower, exhibiting a melting temperature (Tm) reduction of 30 °C compared with the tetrameric mutants and wild‐type PML protein. Furthermore, the exposed surface of the C213R mutation rendered it more prone to protease digestion than that of the C212R mutation. The spectroscopic analysis highlighted ATO‐induced structural alterations in S214L, A216V, and D219H mutants, in contrast to C213R, L217F, and L218P mutations. Moreover, the computational analysis revealed that the ATO‐resistant mutations C213R, A216V, L217F, and L218P caused changes in the size, shape, and flexibility of the PML‐RBCC wild‐type protein. The mutations C213R, A216V, L217F, and L218P destabilize the wild‐type protein structure due to the adaptation of distinct conformational changes. In addition, these mutations disrupt several hydrogen bonds, including interactions involving C212, C213, and C215, which are essential for ATO binding. The local and global structural features induced by these mutations provide mechanistic insight into ATO resistance and APL pathogenesis. [ABSTRACT FROM AUTHOR]

Although S‐nitrosylation of cysteines is a common protein posttranslational modification, little is known about its three‐dimensional structural features. This paper describes a systematic survey of the data available in the Protein Data Bank. Several interesting observations could be made. (1) As a result of radiation damage, S‐nitrosylated cysteines (Snc) are frequently reduced, at least partially. (2) S‐nitrosylation may be a protection against irreversible thiol oxidation; because the NO group of Snc is relatively accessible to the solvent, it may act as a cork to protect the sulfur atoms of cysteines from oxidation by molecular oxygen to sulfenic, sulfinic, and sulfonic acid; moreover, Snc are frequently found at the start or end of helices and strands and this might shield secondary structural elements from unfolding. [ABSTRACT FROM AUTHOR]

Aging is the primary risk factor for the development of numerous human chronic diseases. On a molecular level, it significantly impacts the regulation of protein modifications, leading to the accumulation of degenerative protein modifications (DPMs) such as aberrant serine phosphorylation (p‐Ser) and trioxidized cysteine (t‐Cys) within the proteome. The altered p‐Ser is linked to abnormal cell signaling, while the accumulation of t‐Cys is associated with chronic diseases induced by oxidative stress. Despite this, the potential cross‐effects and functional interplay between these two critical molecular factors of aging remain undisclosed. This study analyzes the aging proteome of wild‐type C57BL/6NTac mice over 2 years using advanced proteomics and bioinformatics. Our objective is to provide a comprehensive analysis of how t‐Cys affects cell signaling and protein structure in the aging process. The results obtained indicate that t‐Cys residues accumulate in the aging proteome, interact with p‐Ser interacting enzymes, as validated in vitro, and alter their structures similarly to p‐Ser. These findings have significant implications for understanding the interplay of oxidative stress and phosphorylation in the aging process. Additionally, they open new venues for further research on the role(s) of these protein modifications in various human chronic diseases and aging, wherein exacerbated oxidation and aberrant phosphorylation are implicated. [ABSTRACT FROM AUTHOR]

MFSD12 functions as a transmembrane protein required for import of cysteine into melanosomes and lysosomes. The MFSD12 locus has been associated with phenotypic variation in skin color across African, Latin American, and East Asian populations. The frequency of a particular MFSD12 coding variant, rs2240751 (MAF = 0.08), has been reported to correlate with solar radiation and occur at highest frequency in Peruvian (PEL MAF = 0.48) and Han Chinese (CHB MAF = 0.40) populations, suggesting it could be causative for associated phenotypic variation in skin color. We have generated a mouse knock‐in allele, Mfsd12Y182H, to model the human missense p.Tyr182His human variant. We demonstrate that the variant transcript is stably expressed and that agouti mice homozygote for the variant allele are viable with an altered coat color. This in vivo data confirms that the MFSD12 p.Tyr182His variant functions as a hypomorphic allele sufficient to alter mammalian pigmentation. [ABSTRACT FROM AUTHOR]