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https://www.readbyqxmd.com/read/28741928/selection-of-effective-htra3-activators-using-combinatorial-chemistry
#1
Magdalena Wysocka, Kamila Sychowska, Natalia Gruba, Łukasz Winiarski, Marcin Skoreński, Mateusz Psurski, Joanna Makowska, Artur Gieldon, Tomasz Wenta, Mirosław Jarząb, Przemyslaw Glaza, Joanna Zdacewicz, Marcin Sieńczyk, Barbara Lipinska, Adam Lesner
Herein we report selection, synthesis and enzymatic evaluation of a peptidomimetic library able to increase proteolytic activity of HtrA3 (high temperature requirement A) protease. Iterative deconvolution in solution of synthesized modified pentapeptides yielded two potent HtrA3 activators acting in the micromolar range (HCOO-CH2O-C6H4-OCH2-CO-Tyr-Asn-Phe-His-Asn-OH and HCOO-CH2O-C6H4-OCH2-CO-Tyr-Asn-Phe-His-Glu-OH). Both compounds increased proteolysis of an artificial HtrA3 substrate over 40-fold in a selective manner...
July 25, 2017: ACS Combinatorial Science
https://www.readbyqxmd.com/read/28741110/biosensor-of-alkaline-phosphatase-based-on-non-fluorescent-fret-of-eu-3-doped-oxide-nanoparticles-and-phosphorylated-peptide-labeled-with-cyanine-dye
#2
Fan Shi Li, Ya Ling Zhang, Xia Bing Li, Bao Lin Li, Yi Feng Liu
Dephosphorylation of biomolecules under the catalysis of alkaline phosphatase (ALP) is a critical physiological process. Abnormal levels of ALP activity have been associated with a number of diseases; thus, a simple and sensitive assay of ALP activity is highly demanded. Herein, to simulate biological conditions, we labeled a hydrosoluble phosphorylated heptapeptide Gly-Pro-Gly-Asn-p-Tyr-Gly-Ala (pGA) with aminated heptamethine cyanine dye (Cy) to give a low fluorescent labeled peptide Cy-pGA. The synthesized Cy-pGA and Eu(3+)-doped oxide Y0...
July 24, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28737392/ligand-strain-and-entropic-effects-on-the-binding-of-macrocyclic-and-linear-inhibitors-molecular-modelling-of-penicillopepsin-complexes
#3
Dimas Suarez, Natalia Diaz
Using extensive molecular dynamics simulations, we investigate the structure and dynamics of the complexes formed between penicillopepsin and two peptidomimetic inhibitors: a linear compound, isovaleryl(P4)-valine(P3)-asparagine(P2)-leucine(P1)-phosphonate-phenilalanine(P1'), and its macrocylic analog that includes a methylene bridge between the Asn(P2) and Phe(P1') side chains. The macrocyclic inhibitor, which has a 420-fold larger affinity than that of the acyclic one, has been considered to lower the entropic penalty for binding...
July 24, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28734097/first-report-of-ser653-asn-mutation-endowing-high-level-resistance-to-imazamox-in-downy-brome-bromus-tectorum-l
#4
Vipan Kumar, Prashant Jha
BACKGROUND: Bromus tectorum L. is one of the most troublesome grass weed species in cropland and non-cropland areas of the northwestern United States. In summer 2016, a B. tectroum accession (R) that survived imazamox at the field-use rate (44 g ha(-1) ) in an imidazolinone-tolerant (IMI-tolerant or Clearfield(™) ) winter wheat field was collected near Hammond, Carter County, MT, USA. The aim of this study was to determine the resistance profile of the B. tectroum R accession to imazamox and other ALS inhibitors, and investigate the mechanism of resistance to imazamox...
July 22, 2017: Pest Management Science
https://www.readbyqxmd.com/read/28732052/protein-asparagine-deamidation-prediction-based-on-structures-with-machine-learning-methods
#5
Lei Jia, Yaxiong Sun
Chemical stability is a major concern in the development of protein therapeutics due to its impact on both efficacy and safety. Protein "hotspots" are amino acid residues that are subject to various chemical modifications, including deamidation, isomerization, glycosylation, oxidation etc. A more accurate prediction method for potential hotspot residues would allow their elimination or reduction as early as possible in the drug discovery process. In this work, we focus on prediction models for asparagine (Asn) deamidation...
2017: PloS One
https://www.readbyqxmd.com/read/28731187/isolation-and-purification-of-novel-peptides-derived-from-sepia-ink-effects-on-apoptosis-of-prostate-cancer-cell-pc%C3%A2-3
#6
Fangfang Huang, Yinwen Jing, Guofang Ding, Zuisu Yang
Novel prostate cancer therapeutics are in high demand. In order to identify potential therapeutic targets, protein from sepia ink was hydrolyzed by utilizing pepsin in an orthogonal array design. Pepsin hydrolysate (SH) obtained at optimal conditions exhibited the highest antitumor activity. Subsequently, a novel antitumor peptide, which was termed SHP, was isolated through ultrafiltration, gel filtration chromatography and reversed phase high‑performance liquid chromatography. The amino acid sequence of SHP was identified as Leu‑Lys‑Glu‑Glu‑Asn‑Arg‑Arg‑Arg‑Arg‑Asp with a molecular mass of 1371...
July 21, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28729420/revisiting-the-substrate-specificity-of-mammalian-%C3%AE-1-6-fucosyltransferase-fut8-reveals-that-it-catalyzes-core-fucosylation-of-n-glycans-lacking-%C3%AE-1-3-arm-glcnac
#7
Qiang Yang, Roushu Zhang, Hui Cai, Lai-Xi Wang
The mammalian α1,6-fucosyltransferase (FUT8) catalyzes the core fucosylation of N-glycans in the biosynthesis of glycoproteins. Previously, intensive in vitro studies with crude extract or purified enzyme concluded that the attachment of a GlcNAc on the α1,3 mannose arm of N-glycan is essential for FUT8 catalyzed core fucosylation. In contrast, we have recently shown that expression of erythropoietin (EPO) in a GnTI-knockout, FUT8 overexpressing cell line results in the production of fully core-fucosylated glycoforms of the oligomannose substrate Man5GlcNAc2, suggesting that FUT8 can catalyze core fucosylation of N-glycans lacking an α1,3arm GlcNAc in cells...
July 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28728455/asparagine-preserves-intestinal-barrier-function-from-lps-induced-injury-and-regulates-crf-crfr-signaling-pathway
#8
Huiling Zhu, Dingan Pi, Weibo Leng, Xiuying Wang, Chien-An Andy Hu, Yongqing Hou, Jianglin Xiong, Chunwei Wang, Qin Qin, Yulan Liu
Stress causes intestinal inflammation and barrier dysfunction. Corticotrophin-releasing factor (CRF)/CRF receptor (CRFR) signaling pathway has been shown to be important for stress-induced intestinal mucosal alteration. L-Asparagine (ASN) is a powerful stimulator of ornithine decarboxylase and cell proliferation in a variety of cell types, including colonic cells. In the present study, we investigated whether dietary ASN supplementation could alleviate the damage of intestinal barrier function caused by LPS through modulation of CRF/CRFR signaling pathway...
January 1, 2017: Innate Immunity
https://www.readbyqxmd.com/read/28722263/ftsad2-and-ftjaz1-regulate-activity-of-the-ftmyb11-transcription-repressor-of-the-phenylpropanoid-pathway-in-fagopyrum-tataricum
#9
Meiliang Zhou, Zhanmin Sun, Mengqi Ding, Maria D Logacheva, Ivan Kreft, Dan Wang, Mingli Yan, Jirong Shao, Yixiong Tang, Yanmin Wu, Xuemei Zhu
Little is known about the molecular mechanism of the R2R3-MYB transcriptional repressors involved in plant phenylpropanoid metabolism. Here, we describe one R2R3-type MYB repressor, FtMYB11 from Fagopyrum tataricum. It contains the SID-like motif GGDFNFDL and it is regulated by both the importin protein 'Sensitive to ABA and Drought 2' (SAD2) and the jasmonates signalling cascade repressor JAZ protein. Yeast two hybrid and bimolecular fluorescence complementation assays demonstrated that FtMYB11 interacts with SAD2 and FtJAZ1...
July 19, 2017: New Phytologist
https://www.readbyqxmd.com/read/28720870/monocyte-adhesion-to-atherosclerotic-matrix-proteins-is-enhanced-by-asn-gly-arg-deamidation
#10
Bamaprasad Dutta, Jung Eun Park, Subodh Kumar, Piliang Hao, Xavier Gallart-Palau, Aida Serra, Yan Ren, Vitaly Sorokin, Chuen Neng Lee, Hee Hwa Ho, Dominique de Kleijn, Siu Kwan Sze
Atherosclerosis arises from leukocyte infiltration and thickening of the artery walls and constitutes a major component of vascular disease pathology, but the molecular events underpinning this process are not fully understood. Proteins containing an Asn-Gly-Arg (NGR) motif readily undergo deamidation of asparagine to generate isoDGR structures that bind to integrin αvβ3 on circulating leukocytes. Here we report the identification of isoDGR motifs in human atherosclerotic plaque components including extracellular matrix (ECM) proteins fibronectin and tenascin C, which have been strongly implicated in human atherosclerosis...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28714227/transepithelial-transport-of-milk-derived-angiotensin-i-converting-enzyme-inhibitory-peptide-with-the-rlsfnp-sequence
#11
Yuxing Guo, Junai Gan, Qian Zhu, Xiaoqun Zeng, Yangying Sun, Zhen Wu, Daodong Pan
BACKGROUND: To exert an antihypertensive effect after oral administration, Angiotensin I-converting enzyme (ACE) inhibitory peptides must remain active after intestinal transport. The purpose of this article is to elucidate the transport permeability and route of ACE inhibitory peptide Arg-Leu-Ser-Phe-Asn-Pro (RLSFNP) across the intestinal epithelium using a Caco-2 cell monolayers. RESULTS: Intact RLSFNP and RLSFNP breakdown fragments F, FNP, SFNP and RLSF were found in RLSFNP transport solution across Caco-2 cell monolayers using ultra-performance liquid chromatography tandem mass (UPLC-MS)...
July 17, 2017: Journal of the Science of Food and Agriculture
https://www.readbyqxmd.com/read/28711271/identification-of-dipeptidyl-peptidase-iv-inhibitory-peptides-from-mare-whey-protein-hydrolysates
#12
J J Song, Q Wang, M Du, X M Ji, X Y Mao
Inhibition of dipeptidyl peptidase-IV (DPP-IV) activity is a promising strategy for treatment of type 2 diabetes. In current study, DPP-IV inhibitory peptides were identified from mare whey protein hydrolysates obtained by papain. The results showed that all the mare whey protein hydrolysates obtained at various hydrolysis durations possessed more potent DPP-IV inhibitory activity in comparison with intact whey protein. The 4-h hydrolysates showed the greatest DPP-IV inhibitory activity with half-maximal inhibitory concentration of 0...
July 12, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28708093/real-time-communication-support-for-underwater-acoustic-sensor-networks-%C3%A2
#13
Rodrigo Santos, Javier Orozco, Matias Micheletto, Sergio F Ochoa, Roc Meseguer, Pere Millan, And Carlos Molina
Underwater sensor networks represent an important and promising field of research due to the large diversity of underwater ubiquitous applications that can be supported by these networks, e.g., systems that deliver tsunami and oil spill warnings, or monitor submarine ecosystems. Most of these monitoring and warning systems require real-time communication in wide area networks that have a low density of nodes. The underwater communication medium involved in these networks is very harsh and imposes strong restrictions to the communication process...
July 14, 2017: Sensors
https://www.readbyqxmd.com/read/28672164/n-glycan-structures-of-%C3%AE-hlh-subunit-of-helix-lucorum-hemocyanin
#14
Lyudmila Velkova, Pavlina Dolashka, Jozef Van Beeumen, Bart Devreese
The carbohydrate structures of molluscan hemocyanins have recently received particular interest due to their specific monosaccharide composition, as well as their immunostimulatory properties and application in clinical studies. For the first time, we investigated N-glycans of the structural subunit β-HlH of hemocyanin isolated from Helix lucorum. In total, 32 different glycans were enzymatically liberated and characterized by tandem mass spectrometry using a Q-Trap mass spectrometer. Our study revealed a highly heterogeneous mixture of glycans with composition Hex3-7HexNAc2-5MeHex0-4Pent0-1Fuc0-1...
June 22, 2017: Carbohydrate Research
https://www.readbyqxmd.com/read/28665109/role-of-site-specific-asparagine-deamidation-in-islet-amyloid-polypeptide-amyloidogenesis-key-contributions-of-residues-14-and-21
#15
Phuong Trang Nguyen, Ximena Zottig, Mathew Sebastiao, Steve Bourgault
Deamidation of an asparagine residue is a spontaneous non-enzymatic post-translational modification that results in the conversion of asparagine into a mixture of aspartic acid and isoaspartic acid. This chemical conversion modulates protein conformation and physicochemical properties, which could lead to protein misfolding and aggregation. In this study, we investigated the effects of site-specific Asn deamidation on the amyloidogenicity of the aggregation-prone peptide islet amyloid polypeptide (IAPP). IAPP is a 37-residue peptidic hormone whose deposition as insoluble amyloid fibrils is closely associated with type 2 diabetes...
July 14, 2017: Biochemistry
https://www.readbyqxmd.com/read/28662101/specific-gene-expression-signatures-induced-by-the-multiple-oncogenic-alterations-that-occur-within-the-pten-pi3k-akt-pathway-in-lung-cancer
#16
Carmela De Marco, Carmelo Laudanna, Nicola Rinaldo, Duarte Mendes Oliveira, Maria Ravo, Alessandro Weisz, Michele Ceccarelli, Elvira Caira, Antonia Rizzuto, Pietro Zoppoli, Donatella Malanga, Giuseppe Viglietto
Hyperactivation of the phosphatydil-inositol-3' phosphate kinase (PI3K)/AKT pathway is observed in most NSCLCs, promoting proliferation, migration, invasion and resistance to therapy. AKT can be activated through several mechanisms that include loss of the negative regulator PTEN, activating mutations of the catalytic subunit of PI3K (PIK3CA) and/or mutations of AKT1 itself. However, number and identity of downstream targets of activated PI3K/AKT pathway are poorly defined. To identify the genes that are targets of constitutive PI3K/AKT signalling in lung cancer cells, we performed a comparative transcriptomic analysis of human lung epithelial cells (BEAS-2B) expressing active mutant AKT1 (AKT1-E17K), active mutant PIK3CA (PIK3CA-E545K) or that are silenced for PTEN...
2017: PloS One
https://www.readbyqxmd.com/read/28661051/n-linked-glycosylation-of-a-subunit-isoforms-is-critical-for-vertebrate-vacuolar-h-atpase-v-atpase-biosynthesis
#17
Sally Esmail, Norbert Kartner, Yeqi Yao, Joo Wan Kim, Reinhart A F Reithmeier, Morris F Manolson
The a subunit of the V0 membrane-integrated sector of human V-ATPase has four isoforms, a1-a4, with diverse and crucial functions in health and disease. They are encoded by four conserved paralogous genes, and their vertebrate orthologs have positionally conserved N-glycosylation sequons within the second extracellular loop, EL2, of the a subunit membrane domain. Previously, we have shown directly that the predicted sequon for the a4 isoform is indeed N-glycosylated. Here we extend our investigation to the other isoforms by transiently transfecting HEK 293 cells to express cDNA constructs of epitope-tagged human a1-a3 subunits, with or without mutations that convert Asn to Gln at putative N-glycosylation sites...
June 29, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28659375/role-of-glutamine-and-interlinked-asparagine-metabolism-in-vessel-formation
#18
Hongling Huang, Saar Vandekeere, Joanna Kalucka, Laura Bierhansl, Annalisa Zecchin, Ulrike Brüning, Asjad Visnagri, Nadira Yuldasheva, Jermaine Goveia, Bert Cruys, Katleen Brepoels, Sabine Wyns, Stephen Rayport, Bart Ghesquière, Stefan Vinckier, Luc Schoonjans, Richard Cubbon, Mieke Dewerchin, Guy Eelen, Peter Carmeliet
Endothelial cell (EC) metabolism is emerging as a regulator of angiogenesis, but the precise role of glutamine metabolism in ECs is unknown. Here, we show that depriving ECs of glutamine or inhibiting glutaminase 1 (GLS1) caused vessel sprouting defects due to impaired proliferation and migration, and reduced pathological ocular angiogenesis. Inhibition of glutamine metabolism in ECs did not cause energy distress, but impaired tricarboxylic acid (TCA) cycle anaplerosis, macromolecule production, and redox homeostasis...
June 28, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28658581/modulation-of-procaspase-7-self-activation-by-pest-amino-acid-residues-of-the-n-terminal-prodomain-and-intersubunit-linker
#19
Juliano Alves, Humberto Miguel Garay-Malpartida, João Marcelo Occhiucci, Jose Belizario
Procaspase-7 zymogen polypeptide is formed by a short prodomain, a large subunit (p20) and a small subunit (p10) connected to an intersubunit linker. Caspase-7 is activated by an initiator caspase -8 and -9 or by autocatalysis after specific cleavage at IQAD198↓S located at intersubunit linker. Previously, we identified that PEST regions made of amino acid residues Pro (P), Glu (E), Asp (D), Ser (S), Thr (T), Asn (N) and Gln (Q) are conserved flanking amino acid residues in the cleavage sites within at prodomain and intersubunit linker of all caspase family members...
June 28, 2017: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/28642445/identification-of-a-cytogenetic-and-molecular-subgroup-of-acute-myeloid-leukemias-showing-sensitivity-to-l-asparaginase
#20
Salvatore Nicola Bertuccio, Salvatore Serravalle, Annalisa Astolfi, Annalisa Lonetti, Valentina Indio, Anna Leszl, Andrea Pession, Fraia Melchionda
L-Asparaginase (L-Asp) is an enzyme that catalyzes the hydrolysis of L-asparagine to L-aspartic acid, and its depletion induces leukemic cell death. L-Asp is an important component of treatment regimens for Acute Lymphoblastic Leukemia (ALL). Sensitivity to L-Asp is due to the absence of L-Asparagine synthetase (ASNS), the enzyme that catalyzes the biosynthesis of L-asparagine. ASNS gene is located on 7q21.3, and its increased expression in ALLs correlates with L-Asp resistance. Chromosome 7 monosomy (-7) is a recurrent aberration in myeloid disorders, particularly in adverse-risk Acute Myeloid Leukemias (AMLs) and therapy-related myeloid neoplasms (t-MN), that leads to a significant downregulation of the deleted genes, including ASNS...
June 19, 2017: Oncotarget
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