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Non-structural protein 1

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https://www.readbyqxmd.com/read/28636874/next-generation-matrix-metalloproteinase-inhibitors-novel-strategies-bring-new-prospects
#1
REVIEW
Maxim Levin, Yael Udi, Inna Solomonov, Irit Sagi
Enzymatic proteolysis of cell surface proteins and extracellular matrix (ECM) is critical for tissue homeostasis and cell signaling. These proteolytic activities are mediated predominantly by a family of proteases termed matrix metalloproteinases (MMPs). The growing evidence in recent years that ECM and non-ECM bioactive molecules (e.g., growth factors, cytokines, chemokines, on top of matrikines and matricryptins) have versatile functions redefines our view on the roles matrix remodeling enzymes play in many physiological and pathological processes, and underscores the notion that ECM proteolytic reaction mechanisms represent master switches in the regulation of critical biological processes and govern cell behavior...
June 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28636597/phase-separation-drives-heterochromatin-domain-formation
#2
Amy R Strom, Alexander V Emelyanov, Mustafa Mir, Dmitry V Fyodorov, Xavier Darzacq, Gary H Karpen
Constitutive heterochromatin is an important component of eukaryotic genomes that has essential roles in nuclear architecture, DNA repair and genome stability, and silencing of transposon and gene expression. Heterochromatin is highly enriched for repetitive sequences, and is defined epigenetically by methylation of histone H3 at lysine 9 and recruitment of its binding partner heterochromatin protein 1 (HP1). A prevalent view of heterochromatic silencing is that these and associated factors lead to chromatin compaction, resulting in steric exclusion of regulatory proteins such as RNA polymerase from the underlying DNA...
June 21, 2017: Nature
https://www.readbyqxmd.com/read/28636358/transferable-atom-centered-potentials-for-the-correction-of-basis-set-incompleteness-errors-in-density-functional-theory
#3
Alberto Otero-de-la-Roza, Gino A DiLabio
Recent progress in the accurate calculation of non-covalent interactions has enabled density-functional theory (DFT) to model systems relevant in biological and supramolecular chemistry. The application of DFT methods using atom-centered Gaussian basis sets to large systems is limited by the number of basis functions required to accurately model thermochemistry and, in particular, weak intermolecular interactions. Basis-set incompleteness error (BSIE) arising from the use of incomplete basis sets leads to erroneous intermolecular energies, bond dissociation energies, and structures...
June 21, 2017: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/28634536/telavancin-a-novel-semisynthetic-lipoglycopeptide-agent-to-counter-the-challenge-of-resistant-gram-positive-pathogens
#4
REVIEW
Biswadeep Das, Chayna Sarkar, Debasmita Das, Amit Gupta, Arnav Kalra, Shubham Sahni
Telavancin (TD-6424), a semisynthetic lipoglycopeptide vancomycin-derivative, is a novel antimicrobial agent developed by Theravance for overcoming resistant Gram-positive bacterial infections, specifically methicillin-resistant Staphylococcus aureus (MRSA). The US Food and Drug Administration (USFDA) had approved telavancin in 2009 for the treatment of complicated skin and skin structure infections (cSSSIs) caused by Gram-positive bacteria, including MRSA (S. aureus, Streptococcus agalactiae, Streptococcus pyogenes, Streptococcus anginosus group, or Enterococcus faecalis)...
March 2017: Therapeutic Advances in Infectious Disease
https://www.readbyqxmd.com/read/28634472/antifungal-activity-against-filamentous-fungi-of-ts1-a-multifunctional-toxin-from-tityus-serrulatus-scorpion-venom
#5
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/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
#6
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/28632757/molecular-mechanism-of-drp1-assembly-studied-in-vitro-by-cryo-electron-microscopy
#7
Kaustuv Basu, Driss Lajoie, Tristan Aumentado-Armstrong, Jin Chen, Roman I Koning, Blaise Bossy, Mihnea Bostina, Attila Sik, Ella Bossy-Wetzel, Isabelle Rouiller
Mitochondria are dynamic organelles that continually adapt their morphology by fusion and fission events. An imbalance between fusion and fission has been linked to major neurodegenerative diseases, including Huntington's, Alzheimer's, and Parkinson's diseases. A member of the Dynamin superfamily, dynamin-related protein 1 (DRP1), a dynamin-related GTPase, is required for mitochondrial membrane fission. Self-assembly of DRP1 into oligomers in a GTP-dependent manner likely drives the division process. We show here that DRP1 self-assembles in two ways: i) in the presence of the non-hydrolysable GTP analog GMP-PNP into spiral-like structures of ~36 nm diameter; and ii) in the presence of GTP into rings composed of 13-18 monomers...
2017: PloS One
https://www.readbyqxmd.com/read/28631170/development-of-a-peptide-elisa-to-discriminate-vaccine-induced-immunity-from-natural-infection-of-hepatitis-a-virus-in-a-phase-iv-study
#8
C Ye, J Luo, X Wang, J Xi, Y Pan, J Chen, X Yang, G Li, Q Sun, J Yang
Hepatitis A virus (HAV) is a highly infectious agent that causes acute liver disease. The infection can trigger the production of antibodies against the structural and non-structural proteins of HAV. Nonetheless, vaccination with an HAV vaccine leads to the production of a primary antibody against the structural proteins. Because the non-structural proteins are only produced during active virus replication, there is no or very little antibody production against the non-structural proteins. However, the current commercial immunoassay cannot distinguish between antibodies produced during natural infection and those from vaccination against HAV...
June 19, 2017: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/28630009/identification-of-two-frataxin-isoforms-in-zea-mays-structural-and-functional-studies
#9
Celeste Buchensky, Manuel Sánchez, Martin Carrillo, Oscar Palacios, Mercè Capdevila, Jose M Domínguez-Vera, Maria V Busi, Sílvia Atrian, Maria A Pagani, Diego F Gomez-Casati
Frataxin is a ubiquitous protein that plays a role in Fe-S cluster biosynthesis and iron and heme metabolism, although its molecular functions are not entirely clear. In non-photosynthetic eukaryotes, frataxin is encoded by a single gene, and the protein localizes to mitochondria. Here we report the presence of two functional frataxin isoforms in Zea mays, ZmFH-1 and ZmFH-2. We confirmed our previous findings regarding plant frataxins: both proteins have dual localization in mitochondria and chloroplasts. Physiological, biochemical and biophysical studies show some differences in the expression pattern, protection against oxidants and in the aggregation state of both isoforms, suggesting that the two frataxin homologs would play similar but not identical roles in plant cell metabolism...
June 16, 2017: Biochimie
https://www.readbyqxmd.com/read/28629383/epitope-mapping-and-characterization-of-a-novel-nsp10-specific-monoclonal-antibody-that-differentiates-genotype-2-prrsv-from-genotype-1-prrsv
#10
Zhibang Zhang, Xuexia Wen, Jianguo Dong, Xinna Ge, Lei Zhou, Hanchun Yang, Xin Guo
BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV), the causative agent of PRRS, has two distinct and highly diverse genotypes (genotype 1 and genotype 2) in the field. Accurate diagnosis and differentiation of the two genotypes of PRRSV are critical to the effective prevention and control of PRRS. The non-structural protein 10 (Nsp10) plays a vital role in viral replication and is one of the most conserved proteins of PRRSV, thus constituting a good candidate for PRRSV diagnosis...
June 19, 2017: Virology Journal
https://www.readbyqxmd.com/read/28628859/structural-and-functional-effects-of-nucleotide-variation-on-the-human-tb-drug-metabolizing-enzyme-arylamine-n-acetyltransferase-1
#11
Ruben Cloete, Wisdom A Akurugu, Cedric J Werely, Paul D van Helden, Alan Christoffels
The human arylamine N-acetyltransferase 1 (NAT1) enzyme plays a vital role in determining the duration of action of amine-containing drugs such as para-aminobenzoic acid (PABA) by influencing the balance between detoxification and metabolic activation of these drugs. Recently, four novel single nucleotide polymorphisms (SNPs) were identified within a South African mixed ancestry population. Modeling the effects of these SNPs within the structural protein was done to assess possible structure and function changes in the enzyme...
June 10, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28626477/in-vitro-evaluation-of-dihydropyridine-3-carbonitriles-as-potential-cytotoxic-agents-through-pim-1-protein-kinase-inhibition
#12
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
#13
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
#14
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/28623690/candidate-cytochrome-p450-genes-for-ethoxyresorufin-o-deethylase-activity-in-oyster-crassostrea-gigas
#15
Marília Nardelli Siebert, Jacó Joaquim Mattos, Guilherme Toledo-Silva, Guilherme Razzera, Afonso Celso Dias Bainy
Vertebrate cytochrome P450 1 (CYP1) enzymes metabolize endogenous and xenobiotic compounds and usually demonstrate a substrate-inducible response. Ethoxyresorufin O-deethylase activity (EROD) is a common method to quantify CYP1 enzymes activity in these organisms. Despite the absence of this gene family in protostomes, CYP1-like genes were identified in several species, even though no evolutionary relationship has been established with the vertebrate CYP1 family. In the present study, EROD activity was evaluated in microsomal fraction of gills, digestive gland and mantle of Crassostrea gigas...
June 9, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28623292/structural-and-biochemical-characterization-of-poly-adp-ribose-polymerase-from-trypanosoma-brucei
#16
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
#17
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/28621755/biophysical-mode-of-action-and-selectivity-analysis-of-allosteric-inhibitors-of-hepatitis-c-virus-hcv-polymerase
#18
Eldar Abdurakhmanov, Sara Øie Solbak, U Helena Danielson
Allosteric inhibitors of hepatitis C virus (HCV) non-structural protein 5B (NS5B) polymerase are effective for treatment of genotype 1, although their mode of action and potential to inhibit other isolates and genotypes are not well established. We have used biophysical techniques and a novel biosensor-based real-time polymerase assay to investigate the mode-of-action and selectivity of four inhibitors against enzyme from genotypes 1b (BK and Con1) and 3a. Two thumb inhibitors (lomibuvir and filibuvir) interacted with all three NS5B variants, although the affinities for the 3a enzyme were low...
June 16, 2017: Viruses
https://www.readbyqxmd.com/read/28619602/optimized-method-for-isolation-of-immature-intracytoplasmic-retroviral-particles-from-mammalian-cells
#19
Hana Langerová, Tomáš Ruml, Michaela Rumlová
To biochemically and structurally characterize viral intracytoplasmic particles (ICAPs), a sample of high purity and homogeneity is usually required. Production of ICAPs in the system closely related to their natural host cells is crucial for the analysis of host-cell binding proteins involved in ICAPs assembly, transport and budding. However, this approach is often hampered by problems with low yield of the ICAPs due to either low expression or fast release from the host cell. Another obstacle may be a low stability or fragility of the intracellular particles...
June 12, 2017: Journal of Virological Methods
https://www.readbyqxmd.com/read/28619118/serum-levels-of-leptin-and-high-molecular-weight-adiponectin-are-inversely-associated-with-radiographic-spinal-progression-in-patients-with-ankylosing-spondylitis-results-from-the-enradas-trial
#20
Agnes Hartl, Joachim Sieper, Uta Syrbe, Joachim Listing, Kay-Geert Hermann, Martin Rudwaleit, Denis Poddubnyy
BACKGROUND: Previous research indicates a role of adipokines in inflammation and osteogenesis. Hence adipokines might also have a pathophysiological role in inflammation and new bone formation in patients with ankylosing spondylitis (AS). The aim of this study was to investigate the role of adipokine serum levels as predictors of radiographic spinal progression in patients with AS. METHODS: A total of 120 patients with definite AS who completed a 2-year follow up in the ENRADAS trial were included in the current study...
June 15, 2017: Arthritis Research & Therapy
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