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https://www.readbyqxmd.com/read/28425917/tapbpr-bridges-udp-glucose-glycoprotein-glucosyltransferase-1-onto-mhc-class-i-to-provide-quality-control-in-the-antigen-presentation-pathway
#1
Andreas Neerincx, Clemens Hermann, Robin Antrobus, Andy van Hateren, Huan Cao, Nico Trautwein, Stefan Stevanović, Tim Elliott, Janet E Deane, Louise H Boyle
Recently we revealed that TAPBPR is a peptide exchange catalyst important for optimal peptide selection by MHC class I molecules. Here we asked if any other co-factors associate with TAPBPR which would explain its effect on peptide selection. We identify an interaction between TAPBPR and UDP-glucose:glycoprotein glucosyltransferase 1 (UGT1), a folding sensor in the calnexin/calreticulin quality control cycle known to regenerate the Glc1Man9GlcNAc2 moiety on glycoproteins. Our results suggest the formation of a multimeric complex, dependent on a conserved cysteine at position 94 in TAPBPR, in which TAPBPR promotes the association of UGT1 with peptide-receptive class I molecules...
April 20, 2017: ELife
https://www.readbyqxmd.com/read/28419599/mycobacterium-tuberculosis-proteasomal-atpase-mpa-has-a-%C3%AE-grasp-domain-that-hinders-docking-with-the-proteasome-core-protease
#2
Yujie Wu, Kuan Hu, Defeng Li, Lin Bai, Shaoqing Yang, Jordan B Jastrab, Shuhao Xiao, Yonglin Hu, Susan Zhang, K Heran Darwin, Tao Wang, Huilin Li
Mycobacterium tuberculosis (Mtb) has a proteasome system that is essential for its ability to cause lethal infections in mice. A key component of the system is the proteasomal adenosine triphosphatase (ATPase) Mpa, which captures, unfolds, and translocates protein substrates into the Mtb proteasome core particle for degradation. Here, we report the crystal structures of near full-length hexameric Mtb Mpa in apo and ADP-bound forms. Surprisingly, the structures revealed a ubiquitin-like β-grasp domain that precedes the proteasome-activating carboxyl terminus...
April 17, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28417460/effect-of-high-fat-diet-and-growth-stage-on-the-diversity-and-composition-of-intestinal-microbiota-in-healthy-bovine-livestock
#3
Shengyin Jiao, Hui Cao, Yue Dai, Junhui Wu, Jia Lv, Renjia Du, Bei Han
BACKGROUND: This study aimed to investigate the composition of bacteria in the bovine rectum and their functions during growth, in relation to different diets. Fecal samples were collected from 6-, 12-, 18- and 24-month cattle fed high-fat diet, and healthy female parents fed regular-diet. Total DNA was amplified (V3-V4 of 16S rRNA) and submitted to barcode-DNA-pyrosequencing. Then, intestinal microbiota profiles and functions were analysed. RESULTS: A total of 114,512 OTUs were detected from the 1,802,243 sequences obtained...
April 18, 2017: Journal of the Science of Food and Agriculture
https://www.readbyqxmd.com/read/28415607/thymoquinone-exerts-potent-growth-suppressive-activity-on-leukemia-through-dna-hypermethylation-reversal-in-leukemia-cells
#4
Jiuxia Pang, Na Shen, Fei Yan, Na Zhao, Liping Dou, Lai-Chu Wu, Christopher L Seiler, Li Yu, Ke Yang, Veronika Bachanova, Eric Weaver, Natalia Y Tretyakova, Shujun Liu
Thymoquinone (TQ), a bioactive constituent of the volatile oil of Monarda fistulosa and Nigella sativa, possesses cancer-specific growth inhibitory effects, but the underlying molecular mechanisms remain largely elusive. We propose that TQ curbs cancer cell growth through dysfunction of DNA methyltransferase 1 (DNMT1). Molecular docking analysis revealed that TQ might interact with the catalytic pocket of DNMT1 and compete with co-factor SAM/SAH for DNMT1 inhibition. In vitro inhibitory assays showed that TQ decreases DNMT1 methylation activity in a dose-dependent manner with an apparent IC50 of 30 nM...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28413646/role-of-malate-dehydrogenase-in-facilitating-lactate-dehydrogenase-to-support-the-glycolysis-pathway-in-tumors
#5
Siavash Mansouri, Ali Shahriari, Hadi Kalantar, Taraneh Moini Zanjani, Mojtaba Haghi Karamallah
High aerobic glycolysis, as one of the hallmarks of cancer cells, requires nicotinamide adenine dinucleotide (NAD(+)) as a vital co-factor, to guarantee the flow of glycolysis. Malate dehydrogenase (MDH), as an important enzyme in cancer metabolism, is a source of NAD(+) additional to lactate dehydrogenase (LDH). The current study aimed to elucidate the kinetic parameters of MDH in human breast cancer and evaluate its supportive role in the glycolysis pathway. The Michaelis-Menten constant (Km) and maximum velocity (Vmax) of MDH were determined in the crude extracts of human breast tumors and healthy tissue samples, which were obtained directly from the operating theatre...
April 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28409545/high-affinity-caspase-4-binding-to-lps-presented-as-high-molecular-mass-aggregates-or-in-outer-membrane-vesicles
#6
Mark A Wacker, Athmane Teghanemt, Jerrold P Weiss, Jason H Barker
Caspases of the non-canonical inflammasome (caspases -4, -5, and -11) directly bind endotoxin (LOS/LPS) and can be activated in the absence of any co-factors. Models of LPS-induced caspase activation have postulated that 1:1 binding of endotoxin monomers to caspase trigger caspase oligomerization and activation, analogous to that established for endotoxin-induced activation of MD-2/TLR4. However, using metabolically radiolabeled LOS and LPS, we now show high affinity and selective binding of caspase-4 to high molecular mass aggregates of purified endotoxin and to endotoxin-rich outer membrane vesicles without formation of 1:1 endotoxin:caspase complexes...
May 2017: Innate Immunity
https://www.readbyqxmd.com/read/28408540/small-kernel2-encodes-a-glutaminase-in-vitamin-b6-biosynthesis-essential-for-maize-seed-development
#7
Yan-Zhuo Yang, Shuo Ding, Yong Wang, Cui-Ling Li, Yun Shen, Robert Meeley, Donald R McCarty, Bao-Cai Tan
Vitamin B6, an essential co-factor for a range of biochemical reactions and a potent antioxidant, plays important roles in plant growth, development, and stress tolerance. Vitamin B6 deficiency causes embryo lethality in Arabidopsis, but the specific role of vitamin B6 synthesis in endosperm development has not been fully addressed, especially in monocot crops where endosperm constitutes the major portion of the grain. Through molecular characterization of a small kernel2 (smk2) mutant in maize, we reveal that vitamin B6 has differential effects on embryogenesis and endosperm development in maize...
April 13, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28406895/the-superfamily-keeps-growing-identification-in-trypanosomatids-of-ribj-the-first-riboflavin-transporter-family-in-protists
#8
Darío E Balcazar, María Cristina Vanrell, Patricia S Romano, Claudio A Pereira, Fernando A Goldbaum, Hernán R Bonomi, Carolina Carrillo
BACKGROUND: Trypanosomatid parasites represent a major health issue affecting hundreds of million people worldwide, with clinical treatments that are partially effective and/or very toxic. They are responsible for serious human and plant diseases including Trypanosoma cruzi (Chagas disease), Trypanosoma brucei (Sleeping sickness), Leishmania spp. (Leishmaniasis), and Phytomonas spp. (phytoparasites). Both, animals and trypanosomatids lack the biosynthetic riboflavin (vitamin B2) pathway, the vital precursor of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) cofactors...
April 13, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28402854/in%C3%A2-vivo-interplay-between-p27-kip1-gata3-atoh1-and-pou4f3-converts-non-sensory-cells-to-hair-cells-in-adult-mice
#9
Bradley J Walters, Emily Coak, Jennifer Dearman, Grace Bailey, Tetsuji Yamashita, Bryan Kuo, Jian Zuo
Hearing loss is widespread and persistent because mature mammalian auditory hair cells (HCs) are nonregenerative. In mice, the ability to regenerate HCs from surrounding supporting cells (SCs) declines abruptly after postnatal maturation. We find that combining p27(Kip1) deletion with ectopic ATOH1 expression surmounts this age-related decline, leading to conversion of SCs to HCs in mature mouse cochleae and after noise damage. p27(Kip1) deletion, independent of canonical effects on Rb-family proteins, upregulated GATA3, a co-factor for ATOH1 that is lost from SCs with age...
April 11, 2017: Cell Reports
https://www.readbyqxmd.com/read/28400133/perioperative-serum-levels-of-procalcitonin-c-reactive-protein-and-leukocytes-in-head-and-neck-free-flaps
#10
S Koerdt, N Rommel, N H Rohleder, S Sandig, G Frohwitter, T Steiner, K D Wolff, M R Kesting
Microvascular free flaps are considered to be the gold standard in reconstructive head and neck surgery. However, reduced postoperative transplant perfusion is one of the serious postoperative complications and calls for close and reliable monitoring. Procalcitonin, C-reactive protein, and leukocytes are closely associated with local and systemic inflammatory reactions and might have prognostic capacity concerning tissue necrosis. This study aimed to evaluate perioperative serum levels of these three biomarkers to assess their potential in postoperative flap monitoring...
April 8, 2017: International Journal of Oral and Maxillofacial Surgery
https://www.readbyqxmd.com/read/28390470/supplementation-of-culture-medium-with-l-carnitine-improves-the-development-and-cryotolerance-of-in-vitro-produced-porcine-embryos
#11
J L Lowe, L K Bartolac, R Bathgate, C G Grupen
Porcine oocytes and embryos contain substantial amounts of lipid, with little known regarding its metabolic role during development. This study investigated the role of lipid metabolism and the interaction between carbohydrate and lipid substrates in porcine embryos. Following in vitro fertilisation, presumptive zygotes were transferred to culture medium supplemented with L-carnitine, a co-factor required for the metabolism of fatty acids. In porcine zygote medium-3 (PZM-3), which contains pyruvate and lactate, 3mM L-carnitine was the only dose that improved cleavage rates compared with the control...
April 10, 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/28382573/serum-global-metabolomics-profiling-reveals-profound-metabolic-impairments-in-patients-with-mps-iiia-and-mps-iiib
#12
Haiyan Fu, Aaron S Meadows, Ricardo J Pineda, Robert P Mohney, Steve Stirdivant, Douglas M McCarty
The monogenic defects in specific lysosomal enzymes in mucopolysaccharidosis (MPS) III lead to lysosomal storage of glycosaminoglycans and complex CNS and somatic pathology, for which the detailed mechanisms remain unclear. In this study, serum samples from patients with MPS IIIA (age 2-9 yr) and MPS IIIB (2-13 yr) and healthy controls (age 2-9 yr) were assayed by global metabolomics profiling of 658 metabolites using mass spectrometry. Significant alterations were detected in 423 metabolites in all MPS III patients, of which 366 (86...
April 5, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28380339/molecular-basis-of-substrate-specific-acetylation-by-n-terminal-acetyltransferase-natb
#13
Haiyan Hong, Yongfei Cai, Shijun Zhang, Hongyan Ding, Haitao Wang, Aidong Han
The NatB N-terminal acetyltransferase specifically acetylates the N-terminal group of substrate protein peptides starting with Met-Asp/Glu/Asn/Gln. How NatB recognizes and acetylates these substrates remains unknown. Here, we report crystal structures of a NatB holoenzyme from Candida albicans in the presence of its co-factor CoA and substrate peptides. The auxiliary subunit Naa25 of NatB forms a horseshoe-like deck to hold specifically its catalytic subunit Naa20. The first two amino acids Met and Asp of a substrate peptide mediate the major interactions with the active site in the Naa20 subunit...
April 4, 2017: Structure
https://www.readbyqxmd.com/read/28359888/characterisation-of-the-fumarate-hydratase-repertoire-in-trypanosoma-cruzi
#14
Ricardo A P de Pádua, Ali Martin Kia, Antonio J Costa-Filho, Shane R Wilkinson, M Cristina Nonato
Nifurtimox and benznidazole represent the only treatments options available targeting Chagas disease, the most important parasitic infection in the Americas. However, use of these is problematic as they are toxic and ineffective against the more severe stages of the disease. In this work, we used a multidisciplinary approach to characterise the fumarases from Trypanosoma cruzi, the causative agent of Chagas Disease. We showed this trypanosome expresses cytosolic and mitochondrial fumarases that via an iron-sulfur cluster mediate the reversible conversion of fumarate to S-malate...
March 27, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28353636/zinc-and-oxidative-stress-current-mechanisms
#15
REVIEW
Dilina do Nascimento Marreiro, Kyria Jayanne Clímaco Cruz, Jennifer Beatriz Silva Morais, Jéssica Batista Beserra, Juliana Soares Severo, Ana Raquel Soares de Oliveira
Oxidative stress is a metabolic dysfunction that favors the oxidation of biomolecules, contributing to the oxidative damage of cells and tissues. This consequently contributes to the development of several chronic diseases. In particular, zinc is one of the most relevant minerals to human health, because of its antioxidant properties. This review aims to provide updated information about the mechanisms involved in the protective role of zinc against oxidative stress. Zinc acts as a co-factor for important enzymes involved in the proper functioning of the antioxidant defense system...
March 29, 2017: Antioxidants (Basel, Switzerland)
https://www.readbyqxmd.com/read/28348373/the-role-of-rhizobial-nifv-and-plant-fen1-homocitrate-synthases-in-aeschynomene-photosynthetic-bradyrhizobium-symbiosis
#16
Nico Nouwen, Jean-François Arrighi, Fabienne Cartieaux, Clémence Chaintreuil, Djamel Gully, Christophe Klopp, Eric Giraud
In the most studied rhizobium-legume interactions, the host plant supplies the symbiont with homocitrate, an essential co-factor of the nitrogenase enzyme complex, via the expression of a nodule-specific homocitrate synthase FEN1. Photosynthetic bradyrhizobia interacting with Nod factor (NF) dependent and NF-independent Aeschynomene legumes are able to synthesize homocitrate themselves as they contain a nifV gene encoding a homocitrate synthase. Here, we show that in the model strain ORS285, nifV is required for free-living and symbiotic dinitrogen fixation with NF-independent Aeschynomene species...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28340958/metabolism-and-acetylation-in-innate-immune-cell-function-and-fate
#17
REVIEW
Alanna M Cameron, Simon J Lawless, Edward J Pearce
Innate immunity is the first line of defense against invading pathogens. Changes in both metabolism and chromatin accessibility contribute to the shaping of these innate immune responses, and we are beginning to appreciate that cross-talk between these two systems plays an important role in determining innate immune cell differentiation and function. In this review we focus on acetylation, a post-translational modification important for both regulating chromatin accessibility by modulating histone function, and for functional regulation of non-histone proteins, which has many links to both immune signaling and metabolism...
October 2016: Seminars in Immunology
https://www.readbyqxmd.com/read/28338444/the-role-of-diet-in-multiple-sclerosis-a-review
#18
Sabrina Esposito, Simona Bonavita, Maddalena Sparaco, Antonio Gallo, Gioacchino Tedeschi
Multiple sclerosis (MS) is a multifactorial, inflammatory, and neurodegenerative disease of the central nervous system, where environmental factors interact with genetic susceptibility. The role of diet on MS has not been comprehensively elucidated; therefore, through an extensive search of relevant literature, this review reports the most significant evidence regarding nutrition as a possible co-factor influencing the inflammatory cascade by acting on both its molecular pathways and gut microbiota. Since nutritional status and dietary habits in MS patients have not been extensively reported, the lack of a scientific-based consensus on dietary recommendation in MS could encourage many patients to experiment alternative dietetic regimens, increasing the risk of malnutrition...
March 24, 2017: Nutritional Neuroscience
https://www.readbyqxmd.com/read/28336347/solution-conformations-of-a-linked-construct-of-the-zika-virus-ns2b-ns3-protease
#19
Mithun C Mahawaththa, Benjamin J G Pearce, Monika Szabo, Bim Graham, Christian D Klein, Christoph Nitsche, Gottfried Otting
The Zika virus presents a serious risk for global health. Crystal structures of different constructs of the Zika virus NS2B-NS3 protease (NS2B-NS3pro) have been determined with the aim to provide a basis for rational drug discovery. In these structures, the C-terminal β-hairpin of NS2B, NS2Bc, was observed to be either disordered (open conformation) or bound to NS3pro complementing the substrate binding site (closed conformation). Enzymatically active constructs of flaviviral NS2B-NS3 proteases commonly used for inhibitor testing contain a covalent peptide linker between NS2B and NS3pro...
June 2017: Antiviral Research
https://www.readbyqxmd.com/read/28332498/a-genome-wide-screen-identifies-yap-wbp2-interplay-conferring-growth-advantage-on-human-epidermal-stem-cells
#20
Gernot Walko, Samuel Woodhouse, Angela Oliveira Pisco, Emanuel Rognoni, Kifayathullah Liakath-Ali, Beate M Lichtenberger, Ajay Mishra, Stephanie B Telerman, Priyalakshmi Viswanathan, Meike Logtenberg, Lisa M Renz, Giacomo Donati, Sven R Quist, Fiona M Watt
Individual human epidermal cells differ in their self-renewal ability. To uncover the molecular basis for this heterogeneity, we performed genome-wide pooled RNA interference screens and identified genes conferring a clonal growth advantage on normal and neoplastic (cutaneous squamous cell carcinoma, cSCC) human epidermal cells. The Hippo effector YAP was amongst the top positive growth regulators in both screens. By integrating the Hippo network interactome with our data sets, we identify WW-binding protein 2 (WBP2) as an important co-factor of YAP that enhances YAP/TEAD-mediated gene transcription...
March 23, 2017: Nature Communications
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