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https://www.readbyqxmd.com/read/28431046/brg1-interacts-with-sox10-to-establish-the-melanocyte-lineage-and-to-promote-differentiation
#1
Himangi G Marathe, Dawn E Watkins-Chow, Matthias Weider, Alana Hoffmann, Gaurav Mehta, Archit Trivedi, Shweta Aras, Tupa Basuroy, Aanchal Mehrotra, Dorothy C Bennett, Michael Wegner, William J Pavan, Ivana L de la Serna
Mutations in SOX10 cause neurocristopathies which display varying degrees of hypopigmentation. Using a sensitized mutagenesis screen, we identified Smarca4 as a modifier gene that exacerbates the phenotypic severity of Sox10 haplo-insufficient mice. Conditional deletion of Smarca4 in SOX10 expressing cells resulted in reduced numbers of cranial and ventral trunk melanoblasts. To define the requirement for the Smarca4 -encoded BRG1 subunit of the SWI/SNF chromatin remodeling complex, we employed in vitro models of melanocyte differentiation in which induction of melanocyte-specific gene expression is closely linked to chromatin alterations...
April 20, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28429994/ileal-endogenous-losses-in-pigs-feeding-a-protein-free-diet-or-diets-with-different-contents-of-casein-or-crystalline-amino-acids
#2
Matej Brestenský, Soňa Nitrayová, Peter Patráš
The common usage of protein-free diets to estimate unspecific AA losses has been criticised as unphysiological and incorrect. Therefore, in this study different diets were tested for the determination of endogenous losses (EL) of amino acids (AA) and nitrogen (N) assuming a complete absorption in the small intestine. Seven cannulated gilts received a protein-free diet (Diet PF) or diets with 3%, 6% or 10% crude protein (CP) from crystalline AA (Diets CA) or casein (Diets CAS) according to a 7 × 7 Latin square design...
June 2017: Archives of Animal Nutrition
https://www.readbyqxmd.com/read/28428613/differential-regulation-of-pkd-isoforms-in-oxidative-stress-conditions-through-phosphorylation-of-a-conserved-tyr-in-the-p-1-loop
#3
Mathias Cobbaut, Rita Derua, Heike Döppler, Hua Jane Lou, Sandy Vandoninck, Peter Storz, Benjamin E Turk, Thomas Seufferlein, Etienne Waelkens, Veerle Janssens, Johan Van Lint
Protein kinases are essential molecules in life and their crucial function requires tight regulation. Many kinases are regulated via phosphorylation within their activation loop. This loop is embedded in the activation segment, which additionally contains the Mg(2+) binding loop and a P + 1 loop that is important in substrate binding. In this report, we identify Abl-mediated phosphorylation of a highly conserved Tyr residue in the P + 1 loop of protein kinase D2 (PKD2) during oxidative stress. Remarkably, we observed that the three human PKD isoforms display very different degrees of P + 1 loop Tyr phosphorylation and we identify one of the molecular determinants for this divergence...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28428192/long-term-efficacy-survival-and-safety-of-177lu-dota0-tyr3-octreotate-in-patients-with-gastroenteropancreatic-and-bronchial-neuroendocrine-tumors
#4
Tessa Brabander, Wouter A Van der Zwan, Jaap Jm Teunissen, Boen L R Kam, Richard A Feelders, Wouter W de Herder, Casper H J van Eijck, Gaston J H Franssen, Eric P Krenning, Dik J Kwekkeboom
Purpose<br /> Bronchial and gastroenteropancreatic neuroendocrine tumors (NETs) are slow-growing tumors, which frequently express somatostatin receptors on their cell membranes. These receptors are targets for therapy with Lutetium-177-labeled somatostatin analogs. We have treated over 1200 patients with peptide receptor radionuclide therapy (PRRT) with (177)Lu-DOTA(0),Tyr(3)]octreotate ((177)Lu-DOTATATE) since the year 2000 and present the results on efficacy, survival and toxicity of this therapy. <p>Patients and methods<br /> For safety analysis, 610 patients treated with a cumulative dose of at least 100 mCi (3...
April 20, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28427904/leishmania-donovani-tyrosyl-trna-synthetase-structure-in-complex-with-a-tyrosyl-adenylate-analog-and-comparisons-with-human-and-protozoan-counterparts
#5
Ximena Barros-Álvarez, Keshia M Kerchner, Cho Yeow Koh, Stewart Turley, Els Pardon, Jan Steyaert, Ranae M Ranade, J Robert Gillespie, Zhongsheng Zhang, Christophe L M J Verlinde, Erkang Fan, Frederick S Buckner, Wim G J Hol
The crystal structure of Leishmania donovani tyrosyl-tRNA synthetase (LdTyrRS) in complex with a nanobody and the tyrosyl adenylate analog TyrSA was determined at 2.75 Å resolution. Nanobodies are the variable domains of camelid heavy chain-only antibodies. The nanobody makes numerous crystal contacts and in addition reduces the flexibility of a loop of LdTyrRS. TyrSA is engaged in many interactions with active site residues occupying the tyrosine and adenine binding pockets. The LdTyrRS polypeptide chain consists of two pseudo-monomers, each consisting of two domains...
April 17, 2017: Biochimie
https://www.readbyqxmd.com/read/28426198/unified-biosynthetic-origin-of-the-benzodipyrrole-subunits-in-cc-1065
#6
Sheng Wu, Xiao-Hong Jian, Hua Yuan, Wen-Bing Jin, Yue Yin, Ling-Yun Wang, Juan Zhao, Gong-Li Tang
CC-1065 is the first characterized member of a family of naturally occurring antibiotics including yatakemycin and duocarmycins with exceptionally potent anti-tumor activity. CC-1065 contains three benzodipyrroles (1a-, 1b- and 1c-) of which 1a-subunit is remarkable by being composed of a cyclopropane ring, and the mechanism for the biological formation of benzodipyrrole rings remains elusive. Previously, biosynthetic studies of CC-1065 were limited to radioactively labelled precursor feeding experiments, which showed that tyrosine (Tyr) and serine (Ser) were incorporated into the two benzodipyrrole (1b- and 1c-) subunits via the same mode but that this was different from the key cyclopropabenzodipyrrole (1a-) subunit with N1-C2-C3 derived from Ser...
April 20, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28425599/the-starch-binding-domain-family-cbm41-an-in-silico-analysis-of-evolutionary-relationships
#7
Štefan Janeček, Katarína Majzlová, Birte Svensson, E Ann MacGregor
Within the CAZy database, there are 81 carbohydrate-binding module (CBM) families. A CBM represents a non-catalytic domain in a modular arrangement of glycoside hydrolases (GHs). The present in silico study has been focused on starch-binding domains from the family CBM41 that are usually part of pullulanases from the α-amylase family GH13. Currently there are more than 1,600 sequences classified in the family CBM41, almost exclusively from Bacteria, and so a study was undertaken in an effort to divide the members into relevant groups (subfamilies) and also to contribute to the evolutionary picture of family CBM41...
April 20, 2017: Proteins
https://www.readbyqxmd.com/read/28423580/procollagen-lysine-2-oxoglutarate-5-dioxygenase-2-promotes-hypoxia-induced-glioma-migration-and-invasion
#8
Yangyang Xu, Lin Zhang, Yuzhen Wei, Xin Zhang, Ran Xu, Mingzhi Han, Bing Huang, Anjing Chen, Wenjie Li, Qing Zhang, Gang Li, Jian Wang, Peng Zhao, Xingang Li
Poor prognosis of glioblastoma multiforme is strongly associated with the ability of tumor cells to invade the brain parenchyma, which is believed to be the major factor responsible for glioblastoma recurrence. Therefore, identifying the molecular mechanisms driving invasion may lead to the development of improved therapies for glioblastoma patients. Here, we investigated the role of procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 (PLOD2), an enzyme catalyzing collagen cross-linking, in the biology of glioblastoma invasion...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421307/an-efficient-and-rapid-method-to-monitor-the-oxidative-degradation-of-protein-pharmaceuticals-probing-tyrosine-oxidation-with-fluorogenic-derivatization
#9
Rupesh Bommana, Olivier Mozziconacci, Y John Wang, Christian Schöneich
PURPOSE: The loss of potency of protein therapeutics can be linked to the oxidation of specific amino acid residues leading to a great variety of oxidative modifications. The comprehensive identification of these oxidative modifications requires high-resolution mass spectrometry analysis, which requires time and expensive resources. Here, we propose a fluorogenic derivatization method of oxidized Tyr and Phe yielding benzoxazole derivatives, as an orthogonal technique for the rapid screening of protein oxidation...
April 18, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28420706/common-structural-features-of-cholesterol-binding-sites-in-crystallized-soluble-proteins
#10
Anna N Bukiya, Alejandro M Dopico
Cholesterol-protein interactions are essential for the architectural organization of cell membranes and for lipid metabolism. While cholesterol-sensing motifs in transmembrane proteins have been identified, little is known about cholesterol recognition by soluble proteins. We reviewed the structural characteristics of binding sites for cholesterol and cholesterol sulfate from crystallographic structures available in the Protein Data Bank. This analysis unveiled key features of cholesterol-binding sites that are present in either all or the majority of sites: i) the cholesterol molecule is generally positioned between protein domains that have an organized secondary structure; ii) the cholesterol hydroxyl/sulfo group is often partnered by Asn, Gln and/or Tyr while the hydrophobic part of cholesterol interacts with Leu, Ile, Val and/or Phe; iii) cholesterol hydrogen-bonding partners are often found on alpha-helices while amino acids that interact with cholesterol hydrophobic core have a slight preference for beta-strands and secondary structure-lacking protein areas; iv) the steroid C21 and 26 constitute the ″hot spots″ most often seen for steroid-protein hydrophobic interactions; v) common ″cold spots″ are C8, 9, 10, 13 and 17, at which contacts with the proteins were not detected...
April 18, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28418429/chemical-constituents-radical-scavenging-activity-and-enzyme-inhibitory-capacity-of-fruits-from-cotoneaster-pannosus-franch
#11
Francisco Les, Víctor López, Giovanni Caprioli, Romilde Iannarelli, Dennis Fiorini, Marzia Innocenti, Maria Bellumori, Filippo Maggi
Cotoneaster pannosus (Rosaceae) is a semievergreen shrub, producing globose dark red pomes, native to China and widely used as an ornamental plant all over the world. Despite its extensive cultivation, little information is available on the chemical composition and biological activities of its fruits. In this work, the analysis of the chemical composition of C. pannosus fruits, in terms of phenolic components, carotenoids and ascorbic acid by HPLC/DAD, HPLC/ESI-MS and MS/MS as well as in terms of macro- and micro-nutrients was performed...
April 18, 2017: Food & Function
https://www.readbyqxmd.com/read/28413197/structure-and-function-of-helicobacter-pylori-caga-the-first-identified-bacterial-protein-involved-in-human-cancer
#12
REVIEW
Masanori Hatakeyama
Chronic infection with Helicobacter pylori cagA-positive strains is the strongest risk factor of gastric cancer. The cagA gene-encoded CagA protein is delivered into gastric epithelial cells via bacterial type IV secretion, where it undergoes tyrosine phosphorylation at the Glu-Pro-Ile-Tyr-Ala (EPIYA) motifs. Delivered CagA then acts as a non-physiological scaffold/hub protein by interacting with multiple host signaling molecules, most notably the pro-oncogenic phosphatase SHP2 and the polarity-regulating kinase PAR1/MARK, in both tyrosine phosphorylation-dependent and -independent manners...
2017: Proceedings of the Japan Academy. Series B, Physical and Biological Sciences
https://www.readbyqxmd.com/read/28410220/reprogramming-induced-by-isoliquiritigenin-diminishes-melanoma-cachexia-through-mtorc2-akt-gsk3%C3%AE-signaling
#13
Xiao-Yu Chen, De-Fang Li, Ji-Chun Han, Bo Wang, Zheng-Ping Dong, Li-Na Yu, Zhao-Hai Pan, Chuan-Jun Qu, Ying Chen, Shi-Guo Sun, Qiu-Sheng Zheng
Isoliquiritigenin (ISL), a member of the flavonoids, is known to have anti-tumor activity in vitro and in vivo. The effect of ISL on reprogramming in cancer cells, however, remains elusive. In this study, we investigated the effect of ISL on reprogramming in human melanoma A375 cells. ISL (15 μg/ml) significantly inhibited A375 cell proliferation, anchorage independent cell proliferation and G2/M cell cycle arrest after ISL exposure for 24 h. However, there were no significant changes in apoptosis rate. Terminal differentiation indicators (melanin content, melanogenesis mRNA expression, tyrosinase (TYR) activity) were all up-regulated by ISL treatment...
March 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28409923/the-catalase-activity-of-catalase-peroxidases-is-modulated-by-changes-in-the-pka-of-the-distal-histidine
#14
Miguel Machuqueiro, Bruno Victor, Jacek Switala, Jacylyn Villanueva, Carme Rovira, Ignacio Fita, Peter C Loewen
The unusual Met-Tyr-Trp adduct composed of cross-linked side chains along with an associated mobile Arg is essential for catalase activity in catalase-peroxidases. In addition, acidic residues in the entrance channel, in particular an Asp and a Glu ∼7 and ∼15 Å, respectively, from the heme, significantly enhance catalase activity. The mechanism by which these channel carboxylates influence catalase activity is the focus of this work. Seventeen new variants with fewer and additional acidic residues have been constructed and characterized structurally and for enzymatic activity, revealing that their effect on activity is roughly inversely proportional to their distance from the heme and adduct, suggesting that the electrostatic potential of the heme cavity may be affected...
April 20, 2017: Biochemistry
https://www.readbyqxmd.com/read/28409541/a-dual-positive-and-negative-regulation-of-monocyte-activation-by-leukocyte-ig-like-receptor-b4-depends-on-the-position-of-the-tyrosine-residues-in-its-itims
#15
Mijeong Park, Robert W Liu, Hongyan An, Carolyn L Geczy, Paul S Thomas, Nicodemus Tedla
The leukocyte Ig-like receptor B4 (LILRB4) is an inhibitory cell surface receptor, primarily expressed on mono-myeloid cells. It contains 2 C-type Ig-like extracellular domains and a long cytoplasmic domain that contains three intracellular immunoreceptor tyrosine-based inhibitory motifs (ITIMs). Data suggest that LILRB4 suppresses Fc receptor-dependent monocyte functions via its ITIMs, but relative contributions of the three ITIMs are not characterised. To address this, tyrosine (Tyr) residues at positions 337, 389 and 419 were single, double or triple mutated to phenylalanine and stably transfected into a human monocytic cell line, THP-1...
May 2017: Innate Immunity
https://www.readbyqxmd.com/read/28406453/sequence-polymorphism-and-intrinsic-structural-disorder-as-related-to-pathobiological-performance-of-the-helicobacter-pylori-caga-oncoprotein
#16
REVIEW
Hiroko Nishikawa, Masanori Hatakeyama
CagA, an oncogenic virulence factor produced by Helicobacter pylori, is causally associated with the development of gastrointestinal diseases such as chronic gastritis, peptic ulcers, and gastric cancer. Upon delivery into gastric epithelial cells via bacterial type IV secretion, CagA interacts with a number of host proteins through the intrinsically disordered C-terminal tail, which contains two repeatable protein-binding motifs, the Glu-Pro-Ile-Tyr-Ala (EPIYA) motif and the CagA multimerization (CM) motif...
April 13, 2017: Toxins
https://www.readbyqxmd.com/read/28404378/axl-molecular-targeting-counteracts-aggressiveness-but-not-platinum-resistance-of-ovarian-carcinoma-cells
#17
Cristina Corno, Laura Gatti, Noemi Arrighetti, Nives Carenini, Nadia Zaffaroni, Cinzia Lanzi, Paola Perego
Ovarian carcinoma, the most common gynecological cancer, is characterized by high lethality mainly due to late diagnosis and treatment failure. The efficacy of platinum drug-based therapy in the disease is limited by the occurrence of drug resistance, a phenomenon often associated with increased metastatic potential. Because the Tyr-kinase receptor Axl can be deregulated in ovarian carcinoma and plays a pro-metastatic/anti-apoptotic role, the aim of this study was to examine if Axl inhibition modulates drug resistance and aggressive features of ovarian carcinoma cells, using various pairs of cisplatin-sensitive and -resistant cell lines...
April 9, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28403215/rv3634c-from-mycobacterium-tuberculosis-h37rv-encodes-an-enzyme-with-udp-gal-glc-and-udp-galnac-4-epimerase-activities
#18
Peehu Pardeshi, K Krishnamurthy Rao, Petety V Balaji
A bioinformatics study revealed that Mycobacterium tuberculosis H37Rv (Mtb) contains sequence homologs of Campylobacter jejuni protein glycosylation enzymes. The ORF Rv3634c from Mtb was identified as a sequence homolog of C. jejuni UDP-Gal/GalNAc 4-epimerase. This study reports the cloning of Rv3634c and its expression as an N-terminal His-tagged protein. The recombinant protein was shown to have UDP-Gal/Glc 4-epimerase activity by GOD-POD assay and by reverse phase HPLC. This enzyme was shown to have UDP-GalNAc 4-epimerase activity also...
2017: PloS One
https://www.readbyqxmd.com/read/28402322/nutritional-status-in-patients-with-phenylketonuria-using-glycomacropeptide-as-their-major-protein-source
#19
A Pinto, M F Almeida, P C Ramos, S Rocha, A Guimas, R Ribeiro, E Martins, A Bandeira, A MacDonald, J C Rocha
BACKGROUND/OBJECTIVES: Low phenylalanine (PHE), glycomacropeptide-based protein substitute (GMP) is an alternative to traditional L-amino acid supplements (AA) used in the dietary management of phenylketonuria (PKU). In a retrospective, longitudinal study, we report the nutritional status of PKU patients taking AA and GMP. SUBJECTS/METHODS: Eleven PKU patients aged 27±10 years (1 HPA, 4 mild and 6 classical PKU) on dietary treatment were evaluated (anthropometry, body composition, blood pressure measurements, biochemical markers including vitamin, mineral, lipids, carbohydrates and protein status/metabolism, and nutritional intake assessment) at two different annual reviews...
April 12, 2017: European Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28402259/the-design-of-novel-inhibitors-for-treating-cancer-by-targeting-cdc25b-through-disruption-of-cdc25b-cdk2-cyclin-a-interaction-using-computational-approaches
#20
Hong-Lian Li, Ying Ma, Ying Ma, Yu Li, Xiu-Bo Chen, Wei-Li Dong, Run-Ling Wang
Cell division cycle 25B is a key cell cycle regulator and widely considered as potent clinical drug target for cancers. This research focused on identifying potential compounds in theory which are able to disrupt transient interactions between CDC25B and its CDK2/Cyclin A substrate.By using the method of ZDOCK and RDOCK, the most optimized 3D structure of CDK2/Cyclin A in complex with CDC25B was constructed and validated using two methods: 1) the superimposition of proteins; 2) analysis of the hydrogen bond distances of Arg 488(N1)-Asp 206(OD1), Arg 492(NE)-Asp 206(OD1), Arg 492(N1)-Asp 206(OD2) and Tyr 497(NE)-Asp 210(OD1)...
March 27, 2017: Oncotarget
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