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Journal of Biological Chemistry

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https://www.readbyqxmd.com/read/28526749/the-origin-and-evolution-of-human-glutaminases-and-their-atypical-c-terminal-ankyrin-repeats
#1
Camila Cristina Pascoal, Zeyaul Islam, Douglas Adamoski, Igor Monteze Ferreira, Ricardo Diogo Righetto, Jefferson Bettini, Rodrigo Villares Portugal, Wyatt W Yue, Ana Gonzalez, Sandra Martha Gomes Dias, Andre Luis Berteli Ambrosio
On the basis of tissue-specific enzyme activity and inhibition by catalytic products, Hans Krebs first demonstrated the existence of multiple glutaminases in mammals. Currently, two human genes are known to encode at least four glutaminase isoforms. However, the phylogeny of these medically relevant enzymes remains unclear, prompting us to investigate their origin and evolution. Using prokaryotic and eukaryotic glutaminase sequences, we built a phylogenetic tree whose topology suggested that the multidomain architecture was inherited from bacterial ancestors, probably simultaneously with the hosting of the proto-mitochondrion endosymbiont...
May 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28526748/the-sialate-o-acetylesterase-esta-from-gut-bacteroidetes-species-enables-sialidase-mediated-cross-species-foraging-of-9-o-acetylated-sialoglycans
#2
Lloyd S Robinson, Warren G Lewis, Amanda L Lewis
The gut harbors many symbiotic, commensal, and pathogenic microbes that engage in the breakdown and metabolism of host carbohydrates. Sialic acids are prominent outermost carbohydrates on mucins and protect underlying glycan chains from enzymatic degradation. Sialidases produced by some members of the colonic microbiota have been shown to promote the expansion of several potential pathogens (e.g. Clostridium difficile, Salmonella, Escherichia coli) that do not produce sialidases. O-acetyl ester modifications of sialic acids help resist the action of many sialidases and are found at high levels in the mammalian colon...
May 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28526747/functional-regions-of-the-peroxin-pex19-necessary-for-peroxisome-biogenesis
#3
Gaurav Agrawal, Helen H Shang, Zhi-Jie Xia, Suresh Subramani
The peroxins Pex19 and Pex3 play an indispensable role in peroxisomal membrane protein (PMP) biogenesis, peroxisome division and inheritance. Pex19 plays multiple roles in these processes, but how these functions relate to the structural organization of the Pex19 domains is unresolved. To this end, using deletion mutants, we mapped the Pex19 regions required for peroxisome biogenesis in the yeast Pichia pastoris. Surprisingly, import-competent peroxisomes still formed when Pex19 domains previously believed to be required for biogenesis were deleted, although the peroxisome size was larger than that in wild-type cells...
May 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28526746/region-specific-proteolysis-differentially-regulates-type-1-inositol-1-4-5-trisphosphate-receptor-activity
#4
Liwei Wang, Larry E Wagner, Kamil J Alzayady, David I Yule
The inositol 1,4,5 trisphosphate receptor (IP3R) is an intracellular Ca2+ release channel expressed predominately on the membranes of the endoplasmic reticulum. IP3R1 can be cleaved by caspase or calpain into at least two receptor fragments. However, the functional consequences of receptor fragmentation are poorly understood. Our previous work has demonstrated that IP3R1 channels, formed following either enzymatic fragmentation or expression of the corresponding complementary polypeptide chains, retain tetrameric architecture and are still activated by IP3 binding, despite the loss of peptide continuity...
May 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28526745/identification-and-characterisation-of-nanobodies-targeting-the-epha4-receptor
#5
Lies Schoonaert, Laura Rué, Bart Roucourt, Mieke Timmers, Susan Little, Lucía Chávez Gutiérrez, Maarten Dewilde, Peter Joyce, Adam Curnock, Peter Weber, Jurgen Haustraete, Gholamreza Hassanzadeh-Ghassabeh, Bart De Strooper, Ludo Van Den Bosch, Philip Van Damme, Robin Lemmens, Wim Robberecht
The ephrin receptor A4 (EphA4) is one of the receptors in the ephrin system that plays a pivotal role in a variety of cell-cell interactions, mostly studied during development. In addition, EphA4 has been found to play a role in cancer biology as well as in the pathogenesis of several neurological disorders such as stroke, spinal cord injury, multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD). Pharmacological blocking of EphA4 has been suggested to be a therapeutic strategy for these disorders...
May 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28522609/coagulation-factor-viia-mediated-protease-activated-receptor-2-activation-leads-to-%C3%AE-catenin-accumulation-via-the-akt-gsk3%C3%AE-pathway-and-contributes-to-breast-cancer-progression
#6
Abhishek Roy, Shabbir A Ansari, Kaushik Das, Ramesh Prasad, Anindita Bhattacharya, Suman Mallik, Asis Mukherjee, Prosenjit Sen
Cell migration and invasion are very characteristic features of cancer cells that promote metastasis, which is one of the most vulnerable causes of mortality among cancer patients. Emerging evidence has shown that coagulation factors can directly mediate cancer associated complications either by enhancing thrombus formation or by initiating various signaling events leading to metastatic cancer progression. It is well-established that apart from its distinct role in blood coagulation, coagulation factor FVIIa enhances aggressive behaviors of breast cancer cells, but the underlying signaling mechanisms still remain elusive...
May 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28522608/altered-learning-memory-and-social-behavior-in-type-1-taste-receptor-subunit-3-knockout-mice-is-associated-with-neuronal-dysfunction
#7
Bronwen Martin, Rui Wang, Wei-Na Cong, Caitlin M Daimon, Wells W Wu, Bin Ni, Kevin G Becker, Elin Lehrmann, William H Wood, Yongqing Zhang, Harmonie Etienne, Jaana van Gastel, Abdelkrim Azmi, Jonathan Janssens, Stuart Maudsley
The type 1 taste receptor member 3 (T1R3) is a G protein-coupled receptor (GPCR) involved in sweet taste perception. Besides the tongue, the T1R3 receptor is highly expressed in brain areas implicated in cognition, including the hippocampus and cortex. As cognitive decline is often preceded by significant metabolic or endocrinological dysfunctions, regulated by the sweet taste perception system, we hypothesized that a disruption of the sweet taste perception in the brain could have a key role in the development of cognitive dysfunction...
May 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28522607/nleb-ssek-effectors-from-citrobacter-rodentium-escherichia-coli-and-salmonella-enterica-display-distinct-differences-in-host-substrate-specificity
#8
Samir El Qaidi, Kangming Chen, Adnan Halim, Lina Siukstaite, Christian Rueter, Ramon Hurtado-Guerrero, Henrik Clausen, Philip R Hardwidge
Many Gram-negative bacterial pathogens use a syringe-like apparatus called a type III secretion system to inject virulence factors into host cells. Some of these effectors are enzymes that modify host proteins to subvert their normal functions. NleB is a glycosyltransferase that modifies host proteins with N-acetyl-D-glucosamine to inhibit antibacterial and inflammatory host responses. NleB is conserved among the attaching/effacing pathogens enterohemorrhagic E. coli (EHEC), enteropathogenic E. coli (EPEC), and Citrobacter rodentium...
May 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28522606/structural-analysis-of-the-dual-function-thioesterase-sav606-unravels-the-mechanism-of-michael-addition-of-glycine-to-an-%C3%AE-%C3%AE-unsaturated-thioester
#9
Taichi Chisuga, Akimasa Miyanaga, Fumitaka Kudo, Tadashi Eguchi
Thioesterases catalyze hydrolysis of acyl thioesters to release carboxylic acid or macrocyclization to produce the corresponding macrocycle in the biosynthesis of fatty acids, polyketides, or nonribosomal peptides. Recently, we reported that the thioesterase CmiS1 from Streptomyces sp. MJ635-86F5 catalyzes the Michael addition of glycine to an α,β-unsaturated fatty acyl thioester followed by thioester hydrolysis in the biosynthesis of the macrolactam antibiotic cremimycin. However, the molecular mechanisms of CmiS1-catalyzed reactions are unclear...
May 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28522605/structure-function-analysis-of-human-sucrase-isomaltase-identifies-key-residues-required-for-catalytic-activity
#10
Birthe Gericke, Natalie Schecker, Mahdi Amiri, Hassan Y Naim
Sucrase-isomaltase (SI) is an intestinal membrane-associated α-glucosidase that breaks down di- and oligosaccharides to absorbable monosaccharides. SI has two homologous functional subunits (sucrase and isomaltase) that both belong to the glycoside hydrolase family 31 (GH31) and differ in substrate specificity. All GH31 enzymes share a consensus sequence harboring an aspartic acid residue as a catalytic nucleophile. Moreover, crystallographic structural analysis of isomaltase predicts that another aspartic acid residue functions as a proton donor in hydrolysis...
May 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28515325/mutual-regulation-between-polo-like-kinase-3-and-siah2-e3-ubiquitin-ligase-defines-a-regulatory-network-that-fine-tunes-the-cellular-response-to-hypoxia-and-nickel
#11
Cen Li, Soyoung Park, Xiaowen Zhang, Wei Dai, Dazhong Xu
Elevated cellular response to hypoxia, which contributes to cell transformation and tumor progression, is a prominent feature of malignant cells in solid tumors. Polo-like kinase 3 (Plk3) is a serine/threonine protein kinase known to inhibit the cellular response to hypoxia and tumorigenesis. Nickel compounds are well established human carcinogens that induce tumorigenesis partly through their hypoxia-mimicking effects. Despite the previous research efforts, the role of Plk3 in the hypoxic response induced by hypoxia or nickel is not completely understood...
May 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28515324/the-diferric-tyrosyl-radical-cluster-of-ribonucleotide-reductase-and-cytosolic-iron-sulfur-clusters-have-distinct-and-similar-biogenesis-requirements
#12
Haoran Li, Martin Stümpfig, Caiguo Zhang, Xiuxiang An, JoAnne Stubbe, Roland Lill, Mingxia Huang
How each metalloprotein assembles the correct metal at the proper binding site presents challenges to the cell. The di-iron enzyme ribonucleotide reductase (RNR) uses a diferric-tyrosyl radical (Fe(III)2-Y·) cofactor to initiate nucleotide reduction. Assembly of this cofactor requires O2, Fe(II), and a reducing equivalent. Recent studies show that RNR cofactor biosynthesis shares the same source of iron, in the form of [2Fe-2S]-GSH2 from the monothiol glutaredoxin Grx3/4, and the same electron source, in the form of the Dre2-Tah18 electron transfer chain, with the cytosolic iron-sulfur protein assembly (CIA) machinery required for maturation of [4Fe-4S] clusters in cytosolic and nuclear proteins...
May 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28515323/%C3%AE-adrenergic-induction-of-lipolysis-in-hepatocytes-is-inhibited-by-ethanol-exposure
#13
Micah B Schott, Karuna Rasineni, Shaun G Weller, Ryan J Schulze, Arthur C Sletten, Carol A Casey, Mark A McNiven
In liver steatosis i.e., fatty liver), hepatocytes accumulate many large neutral lipid-storage organelles known as lipid droplets (LDs). LDs are important in the maintenance of energy homeostasis, but the signaling mechanisms that stimulate LD metabolism in hepatocytes are poorly defined. In adipocytes, catecholamines target the β-adrenergic (β-AR)/cAMP pathway to activate cytosolic lipases and induce their recruitment to the LD surface. Therefore, the goal of this study was to determine whether hepatocytes, like adipocytes, also undergo cAMP-mediated lipolysis in response to β-AR stimulation...
May 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28515322/g%C3%AE-%C3%AE-directly-modulates-vesicle-fusion-by-competing-with-synaptotagmin-for-binding-to-neuronal-snare-proteins-embedded-in-membranes
#14
Zack Zurawski, Brian Page, Michael C Chicka, Rebecca L Brindley, Christopher A Wells, Anita M Preininger, Karren Hyde, James A Gilbert, Osvaldo Cruz-Rodriguez, Kevin P M Currie, Edwin R Chapman, Simon Alford, Heidi E Hamm
Gi/o-coupled GPCRs can inhibit neurotransmitter release at synapses via multiple mechanisms. In addition to Gβγ-mediated modulation of voltage-gated calcium channels(VGCC), inhibition can also be mediated through the direct interaction of Gβγ subunits with the soluble N-ethylmaleimide attachment protein receptor (SNARE) complex of the vesicle fusion apparatus. Binding studies with soluble SNARE complexes have shown that Gβγ binds to both ternary SNARE complexes, t-SNARE heterodimers, and monomeric SNAREs, competing with synaptotagmin(syt)1 for binding sites on t-SNARE...
May 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28515321/flavin-containing-monooxygenases-in-aging-and-disease-emerging-roles-for-ancient-enzymes
#15
Ryan Rossner, Matt Kaeberlein, Scott F Leiser
Flavin- containing monooxygenases (FMOs) are primarily studied as xenobiotic metabolizing enzymes with a prominent role in drug metabolism. In contrast, endogenous functions and substrates of FMOs are less well understood. A growing body of recent evidence, however, implicates FMOs in aging, several diseases, and metabolic pathways. The evidence suggests an important role for these well- conserved proteins in multiple processes and raises questions about the endogenous substrate(s) and regulation of FMOs. Here, we present an overview of evidence for FMOs' involvement in aging and disease, discussing the biological context and arguing for increased investigation into the function of these enzymes...
May 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28515320/recognition-of-nectin-2-by-the-natural-killer-cell-receptor-tigit
#16
Felix A Deuss, Benjamin S Gully, Jamie Rossjohn, Richard Berry
T cell immunoglobulin and ITIM domain (TIGIT) is an inhibitory receptor expressed on the surface of natural killer (NK) cells. TIGIT recognizes nectin and nectin-like adhesion molecules and thus plays a critical role in the innate immune response to malignant transformation. While the TIGIT nectin-like protein-5 (necl-5) interaction is well understood, how TIGIT engages nectin-2, a receptor that is broadly over-expressed in breast and ovarian cancer, remains unknown. Here, we show that TIGIT bound to the immunoglobulin domain of nectin-2 that is most distal from the membrane with an affinity of 6 μM, which was moderately lower than the affinity observed for the TIGIT-necl-5 interaction (3...
May 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28515319/the-h-region-of-twin-arginine-signal-peptides-supports-productive-binding-of-bacterial-tat-precursor-proteins-to-the-tatbc-receptor-complex
#17
Agnes Ulfig, Julia Fröbel, Frank Lausberg, Anne-Sophie Blümmel, Anna Katharina Heide, Matthias Müller, Roland Freudl
The twin arginine translocation (Tat) pathway transports folded proteins across bacterial membranes. Tat precursor proteins possess a conserved twin-arginine (RR) motif in their signal peptides that is involved in their binding to the Tat translocase, but some facets of this interaction remain unclear. Here, we investigated the role of the hydrophobic (h-) region of the Escherichia coli TMAO reductase (TorA) signal peptide in TatBC receptor binding in vivo and in vitro. We show that besides the RR motif, a minimal functional h-region in the signal peptide is required for Tat-dependent export in E...
May 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28515318/molecular-mechanism-of-activation-of-class-ia-phosphoinositide-3-kinases-pi3ks-by-membrane-localized-hras
#18
Braden D Siempelkamp, Manoj K Rathinaswamy, Meredith L Jenkins, John E Burke
Class IA PI3Ks are involved in the generation of the key lipid signaling molecule phosphatidylinositol 3,4,5-trisphosphate (PIP3), and inappropriate activation of this pathway is implicated in a multitude of human diseases, including cancer, inflammation, and primary immunodeficiencies. Class IA PI3Ks are activated downstream of the Ras superfamily of GTPases, and Ras-PI3K interaction plays a key role in promoting tumor formation and maintenance in Ras-driven tumors. Investigating the detailed molecular events in the Ras-PI3K interaction has been challenging because it occurs on a membrane surface...
May 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28515317/characterization-of-a-secretory-hydrolase-from-mycobacterium-tuberculosis-sheds-critical-insight-into-host-lipid-utilization-by-m-tuberculosis
#19
Khundrakpam Herojit Singh, Bhavya Jha, Abhisek Dwivedy, Eira Choudhary, Arpitha G N, Anam Ashraf, Nisheeth Agarwal, Bichitra Kumar Biswal
Mycobacterium tuberculosis causes tuberculosis in humans and predominantly infects alveolar macrophages. To survive inside host lesions and to evade immune surveillance, this pathogen has developed many strategies. For example, M. tuberculosis uses host-derived lipids/fatty acids as nutrients for prolonged persistence within hypoxic host microenvironments. M. tuberculosis imports these metabolites through its respective transporters, and in the case of host fatty acids, a pertinent question arises: does M. tuberculosis have the enzyme(s) for cleavage of fatty acids from host lipids? We show herein that a previously uncharacterized membrane-associated M...
May 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28515316/dna-damage-induced-degradation-of-exo1-limits-dna-end-resection-to-ensure-accurate-dna-repair
#20
Nozomi Tomimatsu, Bipasha Mukherjee, Janelle Louise Harris, Francesca Ludovica Boffo, Molly Hardebeck, Patrick Ryan Potts, Kum Kum Khanna, Sandeep Burma
End resection of DNA double-strand breaks (DSBs) to generate 3'-single-stranded DNA facilitates DSB repair via error-free homologous recombination (HR) while stymieing repair by the error-prone non-homologous end joining (NHEJ) pathway. Activation of DNA end resection involves phosphorylation of the 5' to 3' exonuclease EXO1 by the phosphoinositide 3-kinase-like kinases ATM and ATR, and by the cyclin-dependent kinases 1 and 2. After activation, EXO1 must also be restrained in order to prevent over-resection which is known to hamper optimal HR and trigger global genomic instability...
May 17, 2017: Journal of Biological Chemistry
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