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https://www.readbyqxmd.com/read/28743072/molecular-modeling-and-molecular-dynamics-simulation-study-of-archaeal-leucyl-trna-synthetase-in-complex-with-different-mischarged-trna-in-editing-conformation
#1
A V Rayevsky, M Sharifi, M A Tukalo
Aminoacyl-tRNA synthetases (aaRSs) play important roles in maintaining the accuracy of protein synthesis. Some aaRSs accomplish this via editing mechanisms, among which leucyl-tRNA synthetase (LeuRS) edits non-cognate amino acid norvaline mainly by post-transfer editing. However, the molecular basis for this pathway for eukaryotic and archaeal LeuRS remain unclear. In this study, a complex of archaeal P. horikoshii LeuRS (PhLeuRS) with misacylated tRNA(Leu) was modeled wherever tRNA's acceptor stem was oriented directly into the editing site...
July 18, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28738646/synthesis-characterization-and-application-of-a-novel-multifunctional-stationary-phase-for-hydrophilic-interaction-reversed-phase-mixed-mode-chromatography
#2
Hayriye Aral, K Serdar Çelik, Ramazan Altındağ, Tarık Aral
A novel multifunctional stationary phase based on silica gel was synthesised starting from L- isoleucine and 4-phenylbutylamine and evaluated as a hydrophilic interaction/reversed-phase mixed-mode stationary phase for high-performance liquid chromatography (HPLC). The prepared stationary phase was characterized by elemental analysis, infrared spectroscopy (IR), scanning electron microscopy (SEM), Brunauer, Emmett and Teller (BET) and solid-state (13)C nuclear magnetic resonance (NMR). The mechanisms involved in the chromatographic separation are multi-interaction, including hydrophobic, π-π, hydrogen-bonding, dipole-dipole and ion-dipole interactions...
November 1, 2017: Talanta
https://www.readbyqxmd.com/read/28736524/immune-and-metabolic-regulation-mechanism-of-dangguiliuhuang-decoction-against-insulin-resistance-and-hepatic-steatosis
#3
Hui Cao, Lingling Tuo, Yali Tuo, Ziyun Xia, Rong Fu, Yang Liu, Yihong Quan, Jue Liu, Zhihong Yu, Ming Xiang
Dangguiliuhuang decoction (DGLHD) is a traditional Chinese medicine (TCM) formula, which mainly consists of angelica, radix rehmanniae, radix rehmanniae praeparata, scutellaria baicalensis, coptis chinensis, astragalus membranaceus, and golden cypress, and used for the treatment of diabetes and some autoimmune diseases. In this study, we explored the potential mechanism of DGLHD against insulin resistance and fatty liver in vivo and in vitro. Our data revealed that DGLHD normalized glucose and insulin level, increased the expression of adiponectin, diminished fat accumulation and lipogenesis, and promoted glucose uptake...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28734207/in-silico-designing-of-therapeutic-protein-enriched-with-branched-chain-amino-acids-for-the-dietary-treatment-of-chronic-liver-disease
#4
Sunil L, Prasanna Vasu
Leucine, isoleucine, and valine are three essential branched-chain amino acids (BCAA) account for 40-45% of total essential amino acids. BCAA stimulates protein synthesis primarily in skeletal muscles, and it can directly transport to circulatory blood stream bypassing the liver. Hence, a protein enriched with BCAA is an important therapeutic target for the dietary treatment of chronic liver disease. The present study is to design a synthetic protein enriched with BCAA and the challenge is to maximize the BCAA content, keeping the balanced ratio of leucine, isoleucine, valine - 2: 1: 1...
July 12, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28728917/global-alteration-of-the-drug-binding-pocket-of-human-p-glycoprotein-abcb1-by-substitution-of-fifteen-conserved-residues-reveals-a-negative-correlation-between-substrate-size-and-transport-efficiency
#5
Shahrooz Vahedi, Eduardo E Chufan, Suresh V Ambudkar
P-glycoprotein (P-gp), an ATP-dependent efflux pump, is linked to the development of multidrug resistance in cancer cells. However, the drug-binding sites and translocation pathways of this transporter are not yet well-characterized. We recently demonstrated the important role of tyrosine residues in regulating P-gp ATP hydrolysis via hydrogen bond formations with high affinity modulators. Since tyrosine is both a hydrogen bond donor and acceptor, and non-covalent interactions are key in drug transport, in this study we investigated the global effect of enrichment of tyrosine residues in the drug-binding pocket on the drug binding and transport of P-gp...
July 17, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28726122/beta-ketothiolase-deficiency-presenting-with-metabolic-stroke-after-a-normal-newborn-screen-in-two-individuals
#6
Monica H Wojcik, Klaas J Wierenga, Lance H Rodan, Inderneel Sahai, Sacha Ferdinandusse, Casie A Genetti, Meghan C Towne, Roy W A Peake, Philip M James, Alan H Beggs, Catherine A Brownstein, Gerard T Berry, Pankaj B Agrawal
Beta-ketothiolase (mitochondrial acetoacetyl-CoA thiolase) deficiency is a genetic disorder characterized by impaired isoleucine catabolism and ketone body utilization that predisposes to episodic ketoacidosis. It results from biallelic pathogenic variants in the ACAT1 gene, encoding mitochondrial beta-ketothiolase. We report two cases of beta-ketothiolase deficiency presenting with acute ketoacidosis and "metabolic stroke." The first patient presented at 28 months of age with metabolic acidosis and pallidal stroke in the setting of a febrile gastrointestinal illness...
July 20, 2017: JIMD Reports
https://www.readbyqxmd.com/read/28725161/ep300-single-nucleotide-polymorphism-rs20551-correlates-with-prolonged-overall-survival-in-diffuse-large-b-cell-lymphoma-patients-treated-with-r-chop
#7
Jiao Li, Ning Ding, Xiaogan Wang, Lan Mi, Lingyan Ping, Xuan Jin, Yalu Liu, Zhitao Ying, Yan Xie, Weiping Liu, Yuqin Song, Jun Zhu
BACKGROUND: Rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) is used as standard frontline regimen for diffuse large B-cell lymphoma (DLBCL). The landscape of somatic mutations in DLBCL revealed that inactivation of EP300 plays an important role in lymphomagenesis. A common EP300 single nucleotide polymorphism (SNP) rs20551 results in the substitution of valine for isoleucine at codon 997 close to the Bromodomain. However, the association between SNP rs20551 and clinical prognosis in DLBCL patients treated with R-CHOP is unknown...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28723891/the-lysosomal-potassium-channel-tmem175-adopts-a-novel-tetrameric-architecture
#8
Changkeun Lee, Jiangtao Guo, Weizhong Zeng, Sunghoon Kim, Ji She, Chunlei Cang, Dejian Ren, Youxing Jiang
TMEM175 is a lysosomal K(+) channel that is important for maintaining the membrane potential and pH stability in lysosomes. It contains two homologous copies of a six-transmembrane-helix (6-TM) domain, which has no sequence homology to the canonical tetrameric K(+) channels and lacks the TVGYG selectivity filter motif found in these channels. The prokaryotic TMEM175 channel, which is present in a subset of bacteria and archaea, contains only a single 6-TM domain and functions as a tetramer. Here, we present the crystal structure of a prokaryotic TMEM175 channel from Chamaesiphon minutus, CmTMEM175, the architecture of which represents a completely different fold from that of canonical K(+) channels...
July 19, 2017: Nature
https://www.readbyqxmd.com/read/28719628/salt-tolerant-and-sensitive-alfalfa-medicago-sativa-cultivars-have-large-variations-in-defense-responses-to-the-lepidopteran-insect-spodoptera-litura-under-normal-and-salt-stress-condition
#9
Yunting Lei, Qing Liu, Christian Hettenhausen, Guoyan Cao, Qing Tan, Weiye Zhao, Honghui Lin, Jianqiang Wu
In nature, plants are often exposed to multiple stress factors at the same time. Yet, little is known about how plants modulate their physiology to counteract simultaneous abiotic and biotic stresses, such as soil salinity and insect herbivory. In this study, insect performance bioassays, phytohormone measurements, quantification of transcripts, and protein determination were employed to study the phenotypic variations of two alfalfa (Medicago sativa) cultivars in response to insect Spodoptera litura feeding under normal and salt stress condition...
2017: PloS One
https://www.readbyqxmd.com/read/28717933/a-novel-ms-cleavable-azo-cross-linker-for-peptide-structure-analysis-by-free-radical-initiated-peptide-sequencing-frips
#10
Claudio Iacobucci, Christoph Hage, Mathias Schäfer, Andrea Sinz
The chemical cross-linking/mass spectrometry (MS) approach is a growing research field in structural proteomics that allows gaining insights into protein conformations. It relies on creating distance constraints between cross-linked amino acid side chains that can further be used to derive protein structures. Currently, the most urgent task for designing novel cross-linking principles is an unambiguous and automated assignment of the created cross-linked products. Here, we introduce the homobifunctional, amine-reactive, and water soluble cross-linker azobisimidoester (ABI) as a prototype of a novel class of cross-linkers...
July 17, 2017: Journal of the American Society for Mass Spectrometry
https://www.readbyqxmd.com/read/28717206/an-amino-acid-signature-associated-with-obesity-predicts-2-year-risk-of-hypertriglyceridemia-in-school-age-children
#11
Sofia Moran-Ramos, Elvira Ocampo-Medina, Ruth Gutierrez-Aguilar, Luis Macías-Kauffer, Hugo Villamil-Ramírez, Blanca E López-Contreras, Paola León-Mimila, Joel Vega-Badillo, Roxana Gutierrez-Vidal, Ricardo Villarruel-Vazquez, Erandi Serrano-Carbajal, Blanca E Del-Río-Navarro, Adriana Huertas-Vázquez, Teresa Villarreal-Molina, Isabel Ibarra-Gonzalez, Marcela Vela-Amieva, Carlos A Aguilar-Salinas, Samuel Canizales-Quinteros
Childhood obesity is associated with a number of metabolic abnormalities leading to increased cardiovascular risk. Metabolites can be useful as early biomarkers and new targets to promote early intervention beginning in school age. Thus, we aimed to identify metabolomic profiles associated with obesity and obesity-related metabolic traits. We used data from the Obesity Research Study for Mexican children (ORSMEC) in Mexico City and included a case control (n = 1120), cross-sectional (n = 554) and a longitudinal study (n = 301) of 6-12-year-old children...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28717019/3-hydroxyisobutyryl-coa-hydrolase-involved-in-isoleucine-catabolism-regulates-triacylglycerol-accumulation-in-phaeodactylum-tricornutum
#12
Yufang Pan, Juan Yang, Yangmin Gong, Xiaolong Li, Hanhua Hu
Since methylmalonyl-CoA epimerase appears to be absent in the majority of photosynthetic organisms, including diatoms, (S)-methylmalonyl-CoA, the intermediate of isoleucine (Ile) catabolism, cannot be metabolized to (R)-methylmalonyl-CoA then to succinyl-CoA. In this study, propionyl-CoA carboxylase (PCC) RNAi silenced strains and 3-hydroxyisobutyryl-CoA hydrolase (HIBCH) overexpression strains were constructed to elucidate the Ile degradation pathway and its influence on lipid accumulation in Phaeodactylum tricornutum based on growth, neutral lipid content and metabolite profile analysis...
September 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28716098/awakening-sleeping-beauty-production-of-propionic-acid-in-escherichia-coli-through-the-sbm-operon-requires-the-activity-of-a-methylmalonyl-coa-epimerase
#13
Ricardo Axayacatl Gonzalez-Garcia, Tim McCubbin, Annalena Wille, Manuel Plan, Lars Keld Nielsen, Esteban Marcellin
BACKGROUND: Propionic acid is used primarily as a food preservative with smaller applications as a chemical building block for the production of many products including fabrics, cosmetics, drugs, and plastics. Biological production using propionibacteria would be competitive against chemical production through hydrocarboxylation of ethylene if native producers could be engineered to reach near-theoretical yield and good productivity. Unfortunately, engineering propionibacteria has proven very challenging...
July 17, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/28706879/multiple-substrate-usage-of-coxiella-burnetii-to-feed-a-bipartite-metabolic-network
#14
Ina Häuslein, Franck Cantet, Sarah Reschke, Fan Chen, Matteo Bonazzi, Wolfgang Eisenreich
The human pathogen Coxiella burnetii causes Q-fever and is classified as a category B bio-weapon. Exploiting the development of the axenic growth medium ACCM-2, we have now used (13)C-labeling experiments and isotopolog profiling to investigate the highly diverse metabolic network of C. burnetii. To this aim, C. burnetii RSA 439 NMII was cultured in ACCM-2 containing 5 mM of either [U-(13)C3]serine, [U-(13)C6]glucose, or [U-(13)C3]glycerol until the late-logarithmic phase. GC/MS-based isotopolog profiling of protein-derived amino acids, methanol-soluble polar metabolites, fatty acids, and cell wall components (e...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28705827/3-hydroxyisobutyrate-dehydrogenase-is-involved-in-valine-and-isoleucine-degradation-in-a-thaliana
#15
Peter Schertl, Lennart Danne, Hans-Peter Braun
In plants, amino acid catabolism is especially relevant at metabolic stress situations, e.g. limited carbohydrate availability during extended darkness. Under these conditions, amino acids are used as alternative substrates for respiration. Complete oxidation of the branched chain amino acids (BCAAs) Leucine, Isoleucine and Valine in the mitochondria efficiently allows formation of ATP by oxidative phosphorylation. However, the metabolic pathways for BCAA breakdown are largely unknown so far in plants. A systematic search for Arabidopsis genes encoding proteins resembling enzymes involved in BCAA catabolism in animals, fungi and bacteria as well as proteomic analyses of mitochondrial fractions from Arabidopsis allowed identification of a putative 3-Hydroxyisobutyrate dehydrogenase, AtHDH1 (At4g20930), involved in Valine degradation...
July 13, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28696790/competitive-inhibition-of-amino-acid-transport-in-human-preovulatory-ovarian-follicles
#16
Maciej Jóźwik, Marcin Jóźwik, Anna Justyna Milewska, Frederick C Battaglia, Michał Jóźwik
To date we have yet to examine whether amino acid (AA) transport in human ovarian follicles is affected by competitive inhibition. In contrast, transplacental transfer of AAs in late-gestation sheep is characterized by reciprocal competition. This phenomenon has been described by algebraic equations of umbilical uptake of AAs based on maternal arterial concentrations. In the present translational study at a university teaching hospital, we verified whether these equations apply to the transport of AAs from blood to follicular fluid (FF) in human preovulatory follicles...
July 11, 2017: Systems Biology in Reproductive Medicine
https://www.readbyqxmd.com/read/28696673/how-nothing-boosts-affinity-hydrophobic-ligand-binding-to-the-virtually-vacated-s1-pocket-of-thermolysin
#17
Stefan G Krimmer, Jonathan Cramer, Johannes Schiebel, Andreas Heine, Gerhard Klebe
We investigated the hydration state of the deep, well-accessible hydrophobic S1' specificity pocket of the metalloprotease thermolysin with purposefully designed ligands using high-resolution crystallography and isothermal titration calorimetry. The S1' pocket is known to recognize selectively a very stringent set of aliphatic side chains such as valine, leucine, and isoleucine of putative substrates. We engineered a weak-binding ligand covering the active site of the protease without addressing the S1' pocket, thus transforming it into an enclosed cavity...
July 24, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28694661/relevance-of-proteolysis-and-proteasome-activation-in-fatty-liver-graft-preservation-an-institut-georges-lopez-1-vs-university-of-wisconsin-appraisal
#18
Mohamed Amine Zaouali, Arnau Panisello-Roselló, Alexandre Lopez, Carlos Castro Benítez, Emma Folch-Puy, Agustín García-Gil, Teresa Carbonell, René Adam, Joan Roselló-Catafau
AIM: To compare liver proteolysis and proteasome activation in steatotic liver grafts conserved in University of Wisconsin (UW) and Institut Georges Lopez-1 (IGL-1) solutions. METHODS: Fatty liver grafts from male obese Zücker rats were conserved in UW and IGL-1 solutions for 24 h at 4 °Cand subjected to "ex vivo" normo-thermic perfusion (2 h; 37 °C). Liver proteolysis in tissue specimens and perfusate was measured by reverse-phase high performance liquid chromatography...
June 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28693611/dual-function-of-the-nuclear-export-signal-of-the-borna-disease-virus-nucleoprotein-in-nuclear-export-activity-and-binding-to-viral-phosphoprotein
#19
Mako Yanai, Madoka Sakai, Akiko Makino, Keizo Tomonaga
BACKGROUND: Borna disease virus (BoDV), which has a negative-sense, single-stranded RNA genome, causes persistent infection in the cell nucleus. The nuclear export signal (NES) of the viral nucleoprotein (N) consisting of leucine at positions 128 and 131 and isoleucine at positions 133 and 136 overlaps with one of two predicted binding sites for the viral phosphoprotein (P). A previous study demonstrated that higher expression of BoDV-P inhibits nuclear export of N; however, the function of N NES in the interaction with P remains unclear...
July 11, 2017: Virology Journal
https://www.readbyqxmd.com/read/28690628/comparison-of-salt-tolerance-in-soja-based-on-metabolomics-of-seedling-roots
#20
Mingxia Li, Rui Guo, Yang Jiao, Xiaofei Jin, Haiyan Zhang, Lianxuan Shi
Soybean is an important economic crop that is continually threatened by abiotic stresses, especially salt stress. Wild soybean is an important germplasm resource for the breeding of cultivated soybean. The root system plays a very important role in plant salt tolerance. To explore the salt tolerance-related mechanisms among Soja, we have demonstrated the seedling roots' growth and metabolomics in wild soybean, semi-wild soybean, and cultivated soybean under two types of salt stress by using gas chromatography-mass spectrometry...
2017: Frontiers in Plant Science
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