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Cell Chemical Biology May 2016Every month the editors of Cell Chemical Biology bring you highlights of the most recent chemical biology literature. Our May 2016 selection includes a new method for...
Every month the editors of Cell Chemical Biology bring you highlights of the most recent chemical biology literature. Our May 2016 selection includes a new method for labeling and visualizing nonprotein biomolecules using electron microscopy; a small molecule, originally found in tangerine peel, that regulates our circadian clock and helps with some of the metabolic pathologies associated with circadian rhythms; and a finding that asparagine is used as an amino acid exchanger in tumor cells.
Topics: Animals; Asparagine; Asparagus Plant; Citrus; Flavones; Humans; Mice; Microscopy, Electron
PubMed: 27203369
DOI: 10.1016/j.chembiol.2016.05.007 -
Food Chemistry Nov 2023Coffee is a relevant source of dietary exposure for neoformed furan, alkyl furans and acrylamide. In this study, different statistical methods (hierarchical cluster...
Coffee is a relevant source of dietary exposure for neoformed furan, alkyl furans and acrylamide. In this study, different statistical methods (hierarchical cluster analysis, correlation analysis, partial least squares regression analysis) were used for characterizing the formation of these process contaminants in green coffee beans roasted under the same standardized conditions. The results displayed a strong correlation between sucrose levels and furans in relation to the other sugars analyzed, while acrylamide formation was strongly related to the free asparagine. The data suggest that a sufficiently large amino acid pool in green coffee favors Maillard-induced acrylamide formation from asparagine, while reactions amongst the carbonyl-containing sugar fragmentation products leading to furan formation are suppressed. If the pool of free amino acids is small, it is depleted faster during roasting, thus favoring the formation of furans by caramelization, basically a sugar degradation process in which reactive carbonyl substances are generated and react together.
Topics: Food Handling; Asparagine; Furans; Amino Acids; Sugars; Acrylamide; Hot Temperature; Coffea
PubMed: 37364312
DOI: 10.1016/j.foodchem.2023.136655 -
Prion 2013Prions are self-seeding alternate protein conformations. Most yeast prions contain glutamine/asparagine (Q/N)-rich domains that promote the formation of amyloid-like... (Review)
Review
Prions are self-seeding alternate protein conformations. Most yeast prions contain glutamine/asparagine (Q/N)-rich domains that promote the formation of amyloid-like prion aggregates. Chaperones, including Hsp104 and Sis1, are required to continually break these aggregates into smaller "seeds." Decreasing aggregate size and increasing the number of growing aggregate ends facilitates both aggregate transmission and growth. Our previous work showed that overexpression of 11 proteins with Q/N-rich domains facilitates the de novo aggregation of Sup35 into the [PSI(+)] prion, presumably by a cross-seeding mechanism. We now discuss our recent paper, in which we showed that overexpression of most of these same 11 Q/N-rich proteins, including Pin4C and Cyc8, destabilized pre-existing Q/N rich prions. Overexpression of both Pin4C and Cyc8 caused [PSI(+)] aggregates to enlarge. This is incompatible with a previously proposed "capping" model where the overexpressed Q/N-rich protein poisons, or "caps," the growing aggregate ends. Rather the data match what is expected of a reduction in prion severing by chaperones. Indeed, while Pin4C overexpression does not alter chaperone levels, Pin4C aggregates sequester chaperones away from the prion aggregates. Cyc8 overexpression cures [PSI(+)] by inducing an increase in Hsp104 levels, as excess Hsp104 binds to [PSI(+)] aggregates in a way that blocks their shearing.
Topics: Asparagine; Molecular Chaperones; Prions; Protein Structure, Tertiary; Saccharomyces cerevisiae
PubMed: 23924684
DOI: 10.4161/pri.26021 -
Biochemical and Biophysical Research... Jul 2023The RGD motif on the SARS-CoV-2 spike protein has been suggested to interact with RGD-binding integrins αVβ3 and α5β1 to enhance viral cell entry and alter...
The RGD motif on the SARS-CoV-2 spike protein has been suggested to interact with RGD-binding integrins αVβ3 and α5β1 to enhance viral cell entry and alter downstream signaling cascades. The D405N mutation on the Omicron subvariant spike proteins, resulting in an RGN motif, has recently been shown to inhibit binding to integrin αVβ3. Deamidation of asparagines in protein ligand RGN motifs has been demonstrated to generate RGD and RGisoD motifs that permit binding to RGD-binding integrins. Two asparagines, N481 and N501, on the Wild-type spike receptor-binding domain have been previously shown to have deamidation half-lives of 16.5 and 123 days, respectively, which may occur during the viral life cycle. Deamidation of Omicron subvariant N405 may recover the ability to interact with RGD-binding integrins. Thus, herein, all-atom molecular dynamics simulations of the Wild-type and Omicron subvariant spike protein receptor-binding domains were conducted to investigate the potential for asparagines, the Omicron subvariant N405 in particular, to assume the optimized geometry for deamidation to occur. In summary, the Omicron subvariant N405 was primarily found to be stabilized in a state unfavourable for deamidation after hydrogen bonding with downstream E406. Nevertheless, a small number of RGD or RGisoD motifs on the Omicron subvariant spike proteins may restore the ability to interact with RGD-binding integrins. The simulations also provided structural clarification regarding the deamidation rates of Wild-type N481 and N501 and highlighted the utility of tertiary structure dynamics information in predicting asparagine deamidation. Further work is needed to characterize the effects of deamidation on spike-integrin interactions.
Topics: Humans; COVID-19; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Asparagine; Integrin alphaVbeta3
PubMed: 37178506
DOI: 10.1016/j.bbrc.2023.04.088 -
Ecotoxicology and Environmental Safety Nov 2022Increased production and environmental release of multi-walled carbon nanotubes (MWCNTs) increase soil exposure and potential risk to earthworms. However, MWCNT toxicity...
Increased production and environmental release of multi-walled carbon nanotubes (MWCNTs) increase soil exposure and potential risk to earthworms. However, MWCNT toxicity to earthworms remains unclear, with some studies identifying negative effects and others negligible effects. In this study, to determine whether exposure to MWCNTs negatively affects earthworms and to elucidate possible mechanisms of toxicity, earthworms were exposed to sublethal soil concentrations of MWCNTs (10, 50, and 100 mg/kg) for 28 days. Earthworm growth and reproduction, activities of cytochrome P450 (CYP) isoforms (1A2, 2C9, and 3A4) and antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), and glutathione-s-transferase (GST)), and metabolomics were determined. Effects of MWCNTs on earthworms depended on exposure concentration. Exposure to MWCNTs did not significantly affect growth and reproduction of individual earthworms. Exposure to 50 mg/kg MWCNTs significantly increased activities of CYP2C9, CYP3A4, SOD, CAT, and GST but clearly reduced levels of L-aspartate, L-asparagine, and glutamine. With exposure to 100 mg/kg MWCNTs, toxic effects on earthworms were observed, with significant inhibition in activities of CYP isoenzymes and SOD, significant reductions in L-aspartate, L-asparagine, glutamine, and tryptophan, and simultaneous accumulations of citrate, isocitrate, fumarate, 2-oxoglutarate, pyruvate, D-galactose, carbamoyl phosphate, formyl anthranilate, hypoxanthine, and xanthine. Results suggest that toxicity of MWCNTs to earthworms is associated with reduced detoxification capacity, excessive oxidative stress, and disturbance of multiple metabolic pathways, including amino acids metabolism, the tricarboxylic acid cycle, pyruvate metabolism, D-galactose metabolism, and purine metabolism. The study provides new insights to better understand and predict the toxicity of MWCNTs in soil.
Topics: Animals; Oligochaeta; Nanotubes, Carbon; Soil; Glutamine; Galactose; Aspartic Acid; Asparagine; Oxidative Stress; Superoxide Dismutase; Soil Pollutants; Glutathione Transferase; Reproduction; Pyruvates
PubMed: 36228358
DOI: 10.1016/j.ecoenv.2022.114158 -
Annals of Botany Nov 2016Bromeliads are able to occupy some of the most nutrient-poor environments especially because they possess absorptive leaf trichomes, leaves organized in rosettes,...
BACKGROUND AND AIMS
Bromeliads are able to occupy some of the most nutrient-poor environments especially because they possess absorptive leaf trichomes, leaves organized in rosettes, distinct photosynthetic pathways [C, Crassulacean acid metabolism (CAM) or facultative C-CAM], and may present an epiphytic habit. The more derived features related to these traits are described for the Tillandsioideae subfamily. In this context, the aims of this study were to evaluate how terrestrial predators contribute to the nutrition and performance of bromeliad species, subfamilies and ecophysiological types, whether these species differ in their ecophysiological traits and whether the physiological outcomes are consistent among subfamilies and types (e.g. presence/absence of tank, soil/tank/atmosphere source of nutrients, trichomes/roots access to nutrients).
METHODS
Isotopic (N-enriched predator faeces) and physiological methods (analyses of plant protein, amino acids, growth, leaf mass per area and total N incorporated) in greenhouse experiments were used to investigate the ecophysiological contrasts between Tillandsioideae and Bromelioideae, and among ecophysiological types when a predatory anuran contributes to their nutrition.
KEY RESULTS
It was observed that Bromelioideae had higher concentrations of soluble protein and only one species grew more (Ananas bracteatus), while Tillandsioideae showed higher concentrations of total amino acids, asparagine and did not grow. The ecophysiological types that showed similar protein contents also had similar growth. Additionally, an ordination analysis showed that the subfamilies and ecophysiological types were discrepant considering the results of the total nitrogen incorporated from predators, soluble protein and asparagine concentrations, relative growth rate and leaf mass per area.
CONCLUSIONS
Bromeliad subfamilies showed a trade-off between two strategies: Tillandsioideae stored nitrogen into amino acids possibly for transamination reactions during nutritional stress and did not grow, whereas Bromelioideae used nitrogen for soluble protein production for immediate utilization, possibly for fast growth. These results highlight that Bromeliaceae evolution may be directly associated with the ability to stock nutrients.
Topics: Amino Acids; Ananas; Asparagine; Bromelia; Bromeliaceae; Nitrogen Isotopes; Plant Leaves; Plant Physiological Phenomena; Plant Proteins; Tillandsia
PubMed: 27578765
DOI: 10.1093/aob/mcw174 -
Angewandte Chemie (International Ed. in... Jun 2021Aspartate/asparagine-β-hydroxylase (AspH) is a human 2-oxoglutarate (2OG) and Fe oxygenase that catalyses C3 hydroxylations of aspartate/asparagine residues of...
Aspartate/asparagine-β-hydroxylase (AspH) is a human 2-oxoglutarate (2OG) and Fe oxygenase that catalyses C3 hydroxylations of aspartate/asparagine residues of epidermal growth factor-like domains (EGFDs). Unusually, AspH employs two histidine residues to chelate Fe rather than the typical triad of two histidine and one glutamate/aspartate residue. We report kinetic, inhibition, and crystallographic studies concerning human AspH variants in which either of its Fe binding histidine residues are substituted for alanine. Both the H725A and, in particular, the H679A AspH variants retain substantial catalytic activity. Crystal structures clearly reveal metal-ligation by only a single protein histidine ligand. The results have implications for the functional assignment of 2OG oxygenases and for the design of non-protein biomimetic catalysts.
Topics: Asparagine; Aspartic Acid; Biocatalysis; Crystallography, X-Ray; Ferrous Compounds; Humans; Ligands; Mixed Function Oxygenases; Models, Molecular
PubMed: 33887099
DOI: 10.1002/anie.202103711 -
International Journal of Molecular... Jul 2022Ammonia loss from -asparaginyls is a nonenzymatic reaction spontaneously occurring in all proteins and eventually resulting in damaging isoaspartate residues that hamper...
Ammonia loss from -asparaginyls is a nonenzymatic reaction spontaneously occurring in all proteins and eventually resulting in damaging isoaspartate residues that hamper protein function and induce proteinopathy related to aging. Here, we discuss theoretical considerations supporting the possibility of a full repair reaction and present the first experimental evidence of its existence. If confirmed, the true repair of -asparaginyl deamidation could open new avenues for preventing aging and neurodegenerative diseases.
Topics: Ammonia; Asparagine; Humans; Neurodegenerative Diseases; Proteins
PubMed: 35955504
DOI: 10.3390/ijms23158371 -
Oncotarget Jun 2017Cancer cells reprogram metabolism to coordinate their rapid growth. They addict on glutamine metabolism for adenosine triphosphate generation and macromolecule...
Cancer cells reprogram metabolism to coordinate their rapid growth. They addict on glutamine metabolism for adenosine triphosphate generation and macromolecule biosynthesis. In this study, we report that glutamine deprivation retarded cell growth and induced prosurvival autophagy. Autophagy inhibition by chloroquine significantly enhanced glutamine starvation induced growth inhibition and apoptosis activation. Asparagine deprivation by L-asparaginase exacerbated growth inhibition induced by glutamine starvation and autophagy blockage. Similar to glutamine starvation, inhibition of glutamine metabolism with a chemical inhibitor currently under clinical evaluation was synthetically lethal with chloroquine and L-asparaginase, drugs approved for the treatment of malaria and leukemia, respectively. In conclusion, inhibiting glutaminolysis was synthetically lethal with autophagy inhibition and asparagine depletion. Therefore, targeting glutaminolysis could be a promising approach for colorectal cancer treatment.
Topics: Asparagine; Autophagy; Cell Line, Tumor; Colonic Neoplasms; Glutamine; HEK293 Cells; Humans; Signal Transduction; Sulfides; Thiadiazoles
PubMed: 28424408
DOI: 10.18632/oncotarget.16844 -
Journal of Separation Science Dec 2022Human serum N-linked glycans expression levels change during the disease progression. The low abundance, structural diversity, and coexisting matrices hinder their...
Human serum N-linked glycans expression levels change during the disease progression. The low abundance, structural diversity, and coexisting matrices hinder their detection in mass spectrometry analysis. Considering the hydrophilic nature of N-glycans, cellulose/polymer (1,2-Epoxy-5-hexene) nanohybrid is fabricated with oxirane groups functionalized of asparagine to develop solid phase extraction based hydrophilic interaction liquid chromatography sorbent (cellulose/1,2-Epoxy-5-hexene/asparagine). The morphology, elemental analysis, and surface properties are studied through scanning electron microscopy, energy dispersive X-ray spectroscopy, and Fourier-transform infrared spectroscopy. The large surface area of cellulose/polymer nanohybrid (2.09 × 10 m /g) facilitates the high density of asparagine immobilization resulting in better hydrophilic interaction liquid chromatography enrichment under optimized conditions. The enrichment capability of nanohybrid/asparagine is assessed by the N-Linked glycans released from ovalbumin and immunoglobulin G where 23 and 13 N-glycans are detected respectively. The nanohybrid/asparagine shows selectivity of 1:1200 with spiked bovine serum albumin and sensitivity down to 100 attomole. Human serum profiling for N-glycans identifies 52 glycan structures. This new enrichment strategy enriches serum N-linked glycans in the presence of salts, proteins, endogenous serum peptides, and so forth.
Topics: Humans; Cellulose; Polymers; Asparagine
PubMed: 36168850
DOI: 10.1002/jssc.202200179