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https://www.readbyqxmd.com/read/28634472/antifungal-activity-against-filamentous-fungi-of-ts1-a-multifunctional-toxin-from-tityus-serrulatus-scorpion-venom
#1
Welligton M Santussi, Karla C F Bordon, Ana P N Rodrigues Alves, Camila T Cologna, Suraia Said, Eliane C Arantes
Antimicrobial peptides (AMPs) are ubiquitous and multipotent components of the innate immune defense arsenal used by both prokaryotic and eukaryotic organisms. The search for new AMPs has increased in recent years, due to the growing development of microbial resistance to therapeutical drugs. In this work, we evaluate the effects of Tityus serrulatus venom (Tsv), its fractions and its major toxin Ts1, a beta-neurotoxin, on fungi growth. The fractions were obtained by ion-exchange chromatography of Tsv. The growth inhibition of 11 pathogenic and non-pathogenic filamentous fungi (Aspergillus fumigatus, A...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28634279/in-frame-seven-amino-acid-duplication-in-aip-arose-over-the-last-3000-years-disrupts-protein-interaction-stability-and-is-associated-with-gigantism
#2
Roberto Salvatori, Serban Radian, Yoan Diekmann, Donato Iacovazzo, Alessia David, Plamena Grabovska, Giorgia Grassi, Anna-Marie Bussell, Karen Stals, Astrid Weber, Richard Quinton, Elizabeth Crowne, Valentina Corazzini, Louise A Metherell, Tara Kearney, Daniel Du Plessis, Ajay Sinha, Atik Baborie, Anne-LIse Locoq, Philippe Chanson, Olaf Ansorge, Sian Ellard, Peter J Trainer, David Balding, Mark Thomas, Marta Korbonits
OBJECTIVE: Mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are associated with pituitary adenoma, acromegaly and gigantism. Identical alleles in unrelated pedigrees could be inherited from a common ancestor or result from recurrent mutation events. DESIGN & METHODS: Observational, inferential and experimental study, including: AIP mutation testing; reconstruction of 14 AIP-region (8.3 Mbp) haplotypes; coalescent-based approximate Bayesian estimation of the time to most recent common ancestor (tMRCA) of the derived allele; forward population simulations to estimate current number of allele carriers; proposal of mutation mechanism; protein structure predictions; co-immunoprecipitation and cycloheximide chase experiments...
June 20, 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/28634122/mapping-the-binding-interface-in-a-non-covalent-size-variant-of-a-monoclonal-antibody-using-native-mass-spectrometry-hydrogen-deuterium-exchange-mass-spectrometry-and-computational-analysis
#3
Yuetian Yan, Hui Wei, Sutjano Jusuf, Stanley R Krystek, Jie Chen, Guodong Chen, Richard T Ludwig, Li Tao, Tapan K Das
Variants of monoclonal antibody containing an extra light chain has been reported in protein products(1-3). Due to potential impact on potency and immunogenicity, it is important to understand the formation mechanism of such variants so that appropriate control strategies can be implemented to assure product quality. In a model monoclonal antibody, we observed a size variant with an extra light chain non-covalently associated with the monomer (later named as "1.2mer"). The interaction between monomer and the extra light chain was characterized by native spray and hydrogen/deuterium exchange mass spectrometry (HDX MS) techniques...
June 17, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28633380/epigallocatechin-3-gallate-and-related-phenol-compounds-redirect-the-amyloidogenic-aggregation-pathway-of-ataxin-3-towards-non-toxic-aggregates-and-prevent-toxicity-in-neural-cells-and-caenorhabditis-elegans-animal-model
#4
Cristina Visentin, Francesca Pellistri, Antonino Natalello, Jacopo Vertemara, Marcella Bonanomi, Elena Gatta, Amanda Penco, Annalisa Relini, Luca De Gioia, Cristina Airoldi, Maria E Regonesi, Paolo Tortora
The protein ataxin-3 (ATX3) triggers an amyloid-related neurodegenerative disease when its polyglutamine stretch is expanded beyond a critical threshold. We formerly demonstrated that the polyphenol epigallocatechin-3-gallate (EGCG) could redirect amyloid aggregation of a full-length, expanded ATX3 (ATX3-Q55) towards non-toxic, soluble, SDS-resistant aggregates. Here, we have characterized other related phenol compounds, although smaller in size, i.e., (-)-epigallocatechin gallate (EGC), and gallic acid (GA)...
June 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28631054/adaptation-of-tick-borne-encephalitis-virus-from-human-brain-to-different-cell-cultures-induces-multiple-genomic-substitutions
#5
Eugenia P Ponomareva, Vladimir A Ternovoi, Tamara P Mikryukova, Elena V Protopopova, Anastasia V Gladysheva, Alexander N Shvalov, Svetlana N Konovalova, Eugene V Chausov, Valery B Loktev
The C11-13 strain from the Siberian subtype of tick-borne encephalitis virus (TBEV) was isolated from human brain using pig embryo kidney (PEK), 293, and Neuro-2a cells. Analysis of the complete viral genome of the C11-13 variants during six passages in these cells revealed that the cell-adapted C11-13 variants had multiple amino acid substitutions as compared to TBEV from human brain. Seven out of eight amino acids substitutions in the high-replicating C11-13(PEK) variant mapped to non-structural proteins; 13 out of 14 substitutions in the well-replicating C11-13(293) variant, and all four substitutions in the low-replicating C11-13(Neuro-2a) variant were also localized in non-structural proteins, predominantly in the NS2a (2), NS3 (6) and NS5 (3) proteins...
June 19, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28626477/in-vitro-evaluation-of-dihydropyridine-3-carbonitriles-as-potential-cytotoxic-agents-through-pim-1-protein-kinase-inhibition
#6
Khalil Abnous, Hesam Manavi, Soghra Mehri, Mona Alibolandi, Hossein Kamali, Morteza Ghandadi, Farzin Hadizadeh
PIM-1 protein kinase inhibitor belongs to a novel class of serine/threonine kinases. As PIM-1 is overexpressed in cancer cells and possesses oncogenic functions, its inhibition provides a new option in cancer therapy. In this study, in vitro inhibitory effects of seven analogues of 1, 2-dihydropyridine-3-carbonitrile derivatives Ia-c, IIa-d on the activity of recombinant PIM-1 were evaluated using dimethylthiazol diphenyltetrazolium bromide (MTT) assay. The PIM-1 protein kinase inhibitory potencies and the cytotoxicity effects of tested compounds were respectively as follows: Ic > IIa > Ia > IIb > Ib > IId > IIc and IIb > IIa > Ia > IIc > Ic > Ib > IId, respectively...
June 2017: Research in Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28624391/efficacy-of-melatonin-il-25-and-siil-17b-in-tumorigenesis-associated-properties-of-breast-cancer-cell-lines
#7
Gabriela Bottaro Gelaleti, Thaiz Ferraz Borin, Larissa Bazela Maschio-Signorini, Marina Gobbe Moschetta, Bruna Victorasso Jardim-Perassi, Guilherme Berto Calvinho, Mariana Castilho Facchini, Alicia M Viloria-Petit, Debora Aparecida Pires de Campos Zuccari
Mammary tumorigenesis can be modulated by melatonin, which has oncostatic action mediated by multiple mechanisms, including the inhibition of the activity of transcription factors such as NF-κB and modulation of interleukins (ILs) expression. IL-25 is an active cytokine that induces apoptosis in tumor cells due to differential expression of its receptor (IL-17RB). IL-17B competes with IL-25 for binding to IL-17RB in tumor cells, promoting tumorigenesis. This study purpose is to address the possibility of engaging IL-25/IL-17RB signaling to enhance the effect of melatonin on breast cancer cells...
June 14, 2017: Life Sciences
https://www.readbyqxmd.com/read/28624389/plasma-proteome-analysis-in-patients-with-pulmonary-arterial-hypertension-an-observational-cohort-study
#8
Christopher J Rhodes, John Wharton, Pavandeep Ghataorhe, Geoffrey Watson, Barbara Girerd, Luke S Howard, J Simon R Gibbs, Robin Condliffe, Charles A Elliot, David G Kiely, Gerald Simonneau, David Montani, Olivier Sitbon, Henning Gall, Ralph T Schermuly, H Ardeschir Ghofrani, Allan Lawrie, Marc Humbert, Martin R Wilkins
BACKGROUND: Idiopathic and heritable pulmonary arterial hypertension form a rare but molecularly heterogeneous disease group. We aimed to measure and validate differences in plasma concentrations of proteins that are associated with survival in patients with idiopathic or heritable pulmonary arterial hypertension to improve risk stratification. METHODS: In this observational cohort study, we enrolled patients with idiopathic or heritable pulmonary arterial hypertension from London (UK; cohorts 1 and 2), Giessen (Germany; cohort 3), and Paris (France; cohort 4)...
June 14, 2017: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/28623292/structural-and-biochemical-characterization-of-poly-adp-ribose-polymerase-from-trypanosoma-brucei
#9
Teemu Haikarainen, Mariana Schlesinger, Ezeogo Obaji, Silvia H Fernández Villamil, Lari Lehtiö
Trypanosoma brucei is a unicellular parasite responsible for African trypanosomiasis or sleeping sickness. It contains a single PARP enzyme opposed to many higher eukaryotes, which have numerous PARPs. PARPs are responsible for a post-translational modification, ADP-ribosylation, regulating a multitude of cellular events. T. brucei PARP, like human PARPs-1-3, is activated by DNA binding and it potentially functions in DNA repair processes. Here we characterized activation requirements, structure and subcellular localization of T...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28622512/structural-basis-of-egg-coat-sperm-recognition-at-fertilization
#10
Isha Raj, Hamed Sadat Al Hosseini, Elisa Dioguardi, Kaoru Nishimura, Ling Han, Alessandra Villa, Daniele de Sanctis, Luca Jovine
Recognition between sperm and the egg surface marks the beginning of life in all sexually reproducing organisms. This fundamental biological event depends on the species-specific interaction between rapidly evolving counterpart molecules on the gametes. We report biochemical, crystallographic, and mutational studies of domain repeats 1-3 of invertebrate egg coat protein VERL and their interaction with cognate sperm protein lysin. VERL repeats fold like the functionally essential N-terminal repeat of mammalian sperm receptor ZP2, whose structure is also described here...
June 15, 2017: Cell
https://www.readbyqxmd.com/read/28618224/design-synthesis-and-structure-activity-relationship-of-tetrahydropyrido-4-3-d-pyrimidine-derivatives-as-potent-smoothened-antagonists-with-in-vivo-activity
#11
Wenfeng Lu, Yongqiang Liu, Haikuo Ma, Jiyue Zheng, Sheng Tian, Zhijian Sun, Lusong Luo, Jiajun Li, Hongjian Zhang, Zeng-Jie Yang, Xiaohu Zhang
Medulloblastoma is one of the most prevalent brain tumors in children. Aberrant hedgehog (Hh) pathway signaling is thought to be involved in the initiation and development of medulloblastoma. Vismodegib, the first FDA-approved cancer therapy based on inhibition of aberrant hedgehog signaling, targets smoothened (Smo), a G-protein coupled receptor (GPCR) central to the Hh pathway. Although vismodegib exhibits promising therapeutic efficacy in tumor treatment, concerns have been raised from its non-linear pharmacokinetic (PK) profiles at high doses partly due to low aqueous solubility...
June 15, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28615203/phosphorylation-of-serine-225-in-hepatitis-c-virus-ns5a-regulates-protein-protein-interactions
#12
Niluka Goonawardane, Anna Gebhardt, Christopher Bartlett, Andreas Pichlmair, Mark Harris
Hepatitis C virus (HCV) non-structural protein 5A (NS5A) is a phosphoprotein that plays key, yet poorly defined, roles in both virus genome replication and virion assembly/release. It has been proposed that differential phosphorylation could act as a switch to regulate the various functions of NS5A, however the mechanistic details of the role of this post-translational modification in the virus life cycle remains obscure. We previously reported (Ross-Thriepland et al, 2015) a role for phosphorylation at serine 225 (S225) of NS5A in the regulation of JFH-1 (genotype 2a) genome replication...
June 14, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28613877/x-ray-emission-spectroscopy-of-the-proteinogenic-amino-acids-at-all-relevant-absorption-edges
#13
Frank Meyer, Monika Blum, Andreas Benkert, Dirk Hauschild, Yekkoni Lakshmanan Jeyachandran, Regan G Wilks, Wanli Yang, Marcus Bär, Clemens Heske, Friedrich Reinert, Michael Zharnikov, Lothar Weinhardt
Non-resonant N K, O K, C K, and S L2,3 X-ray emission spectra (XES) of the 20 most common proteinogenic amino acids in their solid zwitterionic form are reported. They represent a comprehensive database, which can serve as a reliable basis for XES studies of peptides and proteins. At the most important N and O K-edges, clear similarities and differences between the spectra of certain amino acids are observed and associated with the specific chemical structure of these molecules and their functional groups. Analysis of these spectra allows generating spectral fingerprints of the protonated amino group, the deprotonated carboxylic group, and, using a building block approach, of the specific nitrogen- and oxygen-containing functional groups in the side chains of the amino acids...
June 14, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28606543/structural-investigations-on-arabinogalactan-proteins-from-a-lycophyte-and-different-monilophytes-ferns-in-the-evolutionary-context
#14
Desirée Bartels, Birgit Classen
Today, understanding of cell wall evolution is incomplete due to limited knowledge of cell wall structure of non-flowering plants. Besides polysaccharides, proteoglycans like arabinogalactan-proteins are important constituents of the cell wall of most if not all seed plants. This article provides the first detailed characterization of AGPs from a lycophyte and different ferns, which are the closest living relatives to seed plants. The amount of protein in fern AGPs (6-12%) was in a range comparable to most seed plant AGPs...
September 15, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28595551/nmr-based-drug-development-and-improvement-against-malignant-melanoma-implications-for-the-mia-protein-family
#15
Oliver Arnolds, Xueyin Zhong, King Tuo Yip, Miriam Schöpel, Bastian Kohl, Stefanie Pütz, Raid Abdel-Jalil, Raphael Stoll
The Melanoma Inhibitory Activity (MIA) protein is strongly expressed and secreted by malignant melanoma cells and was shown to promote melanoma development and invasion. The MIA protein was the first extracellular protein shown to adopt a Src homology 3 (SH3) domain-like fold in solution that can bind to fibronectin type III domains. Together with MIA, the homologous proteins OTOR (or FDP), MIA-2, and TANGO (or MIA-3) constitute a protein family of non-cytoplasmic and - except for full-length TANGO and TANGO1-like (TALI) - extracellular SH3-domain containing proteins...
June 8, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28595540/apicoplast-import-protein-tic20-a-promising-therapeutic-molecular-target-for-plasmodium-falciparum-an-insilico-approach-for-therapeutic-intervention
#16
Pavan C P K Srimath-Tirumala-Peddinti, Sandeep Solmon Kusuma, Deepthi Nammi, Nageswara Rao Reddy Neelapu
Malaria is a lethal disease causing mortality to over millions each year. Drug resistance in the malarial parasite encouraged to discover effective antimalarial drug targets and drugs. An objective of this current study is to identify drug targets for malarial parasite. Genes unique, non-homologous to humans and essential for parasite are identified using BLASTn by comparing genomes between parasite and host. Further open BLASTp was used to filter the targets specific to Plasmodium species and later were subjected to gene property analysis to identify 65 potential targets...
June 5, 2017: Infectious Disorders Drug Targets
https://www.readbyqxmd.com/read/28594932/ns5a-inhibitors-unmask-differences-in-functional-replicase-complex-half-life-between-different-hepatitis-c-virus-strains
#17
Tiffany Benzine, Ryan Brandt, William C Lovell, Daisuke Yamane, Petra Neddermann, Raffaele De Francesco, Stanley M Lemon, Alan S Perelson, Ruian Ke, David R McGivern
Hepatitis C virus (HCV) RNA is synthesized by the replicase complex (RC), a macromolecular assembly composed of viral non-structural proteins and cellular co-factors. Inhibitors of the HCV NS5A protein block formation of new RCs but do not affect RNA synthesis by pre-formed RCs. Without new RC formation, existing RCs turn over and are eventually lost from the cell. We aimed to use NS5A inhibitors to estimate the half-life of the functional RC of HCV. We compared different cell culture-infectious strains of HCV that may be grouped based on their sensitivity to lipid peroxidation: robustly replicating, lipid peroxidation resistant (LPOR) viruses (e...
June 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28594382/coralsnake-venomics-analyses-of-venom-gland-transcriptomes-and-proteomes-of-six-brazilian-taxa
#18
Steven D Aird, Nelson Jorge da Silva, Lijun Qiu, Alejandro Villar-Briones, Vera Aparecida Saddi, Mariana Pires de Campos Telles, Miguel L Grau, Alexander S Mikheyev
Venom gland transcriptomes and proteomes of six Micrurus taxa (M. corallinus, M. lemniscatus carvalhoi, M. lemniscatus lemniscatus, M. paraensis, M. spixii spixii, and M. surinamensis) were investigated, providing the most comprehensive, quantitative data on Micrurus venom composition to date, and more than tripling the number of Micrurus venom protein sequences previously available. The six venomes differ dramatically. All are dominated by 2-6 toxin classes that account for 91-99% of the toxin transcripts...
June 8, 2017: Toxins
https://www.readbyqxmd.com/read/28586716/design-synthesis-and-characterization-of-novel-quinacrine-analogs-that-preferentially-kill-cancer-over-non-cancer-cells-through-the-down-regulation-of-bcl-2-and-up-regulation-of-bax-and-bad
#19
V Raja Solomon, Danah Almnayan, Hoyun Lee
Both quinacrine, which contains a 9-aminoacridine scaffold, and thiazolidin-4-one are promising anticancer leads. In an attempt to develop effective and potentially safe anticancer agents, we synthesized 23 novel hybrid compounds by linking the main structural unit of the 9-aminoacridine ring with the thiazolidin-4-one ring system, followed by examination of their anticancer effects against three human breast tumor cell lines and matching non-cancer cells. Most of the hybrid compounds showed good activities, and many of them possessed the preferential killing property against cancer over non-cancer cells...
May 27, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28586211/structure-based-design-of-n-3-1h-pyrazolo-3-4-b-pyridin-5-yl-ethynyl-benzenesulfonamides-as-selective-leucine-zipper-and-sterile-%C3%AE-motif-kinase-zak-inhibitors
#20
Yu Chang, Xiaoyun Lu, Marthandam Asokan Shibu, Yi-Bo Dai, Jinfeng Luo, Yan Zhang, Yingjun Li, Peng Zhao, Zhang Zhang, Yong Xu, Zheng-Chao Tu, Qingwen Zhang, Cai-Hong Yun, Chih-Yang Huang, Ke Ding
A series of N-(3-((1H-pyrazolo[3, 4-b]pyridin-5-yl)ethynyl) benzenesulfonamides were rationally designed as highly selective ZAK inhibitors. One of the most promising compound 1h strongly inhibits the kinase activity of ZAK with an IC50 value of 3.3 nM, and dose-dependently suppresses the activation of ZAK downstream signals both in vitro and in vivo. However, the compound is significantly less potent for a majority of the 403 non-mutated kinases evaluated. A high resolution complex crystal structure was further determined to elucidate the detail interaction between an inhibitor and ZAK protein...
June 6, 2017: Journal of Medicinal Chemistry
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