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Non-structural protein 1

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https://www.readbyqxmd.com/read/28210927/efficacy-and-safety-of-daclatasvir-plus-pegylated-interferon-alfa-2a-and-ribavirin-in-previously-untreated-hcv-subjects-coinfected-with-hiv-and-hcv-genotype-1-a-phase-iii-open-label-study
#1
Mark S Sulkowski, Walford J Fessel, Adriano Lazzarin, Juan Berenguer, Natalia Zakharova, Hugo Cheinquer, Pierre Côté, Douglas Dieterich, Adrian Gadano, Gail Matthews, Jean-Michel Molina, Christophe Moreno, Juan Antonio Pineda, Federico Pulido, Antonio Rivero, Jurgen Rockstroh, Dennis Hernandez, Fiona McPhee, Timothy Eley, Zhaohui Liu, Patricia Mendez, Eric Hughes, Stephanie Noviello, Peter Ackerman
BACKGROUND: Daclatasvir (DCV) is a potent, pangenotypic, hepatitis C virus (HCV) non-structural protein 5A inhibitor with low potential for drug interactions with antiretroviral therapy (ART). We evaluated the safety and efficacy of DCV plus peginterferon alfa-2a/ribavirin (PegIFN/RBV) in HIV-1/HCV genotype-1-coinfected patients. METHODS: AI444043 (NCT01471574), an open-label, Phase III, single-arm, response-guided treatment (RGT) study included 301 patients. They received DCV doses of 30, 60 or 90 mg once daily (depending on concomitant ART), plus weight-based RBV (<75 kg, 1000 mg/day; or ≥75 kg, 1200 mg/day), and once-weekly PegIFN 180 μg, for 24 weeks...
February 16, 2017: Hepatology International
https://www.readbyqxmd.com/read/28209172/evaluation-of-the-contribution-of-the-transmembrane-region-to-the-ectodomain-conformation-of-the-human-immunodeficiency-virus-hiv-1-envelope-glycoprotein
#2
Hanh T Nguyen, Navid Madani, Haitao Ding, Emerald Elder, Amy Princiotto, Christopher Gu, Patrice Darby, James Alin, Alon Herschhorn, John C Kappes, Youdong Mao, Joseph G Sodroski
BACKGROUND: The human immunodeficiency virus (HIV-1) envelope glycoprotein (Env), a Type 1 transmembrane protein, assembles into a trimeric spike complex that mediates virus entry into host cells. The high potential energy of the metastable, unliganded Env trimer is maintained by multiple non-covalent contacts among the gp120 exterior and gp41 transmembrane Env subunits. Structural studies suggest that the gp41 transmembrane region forms a left-handed coiled coil that contributes to the Env trimer interprotomer contacts...
February 16, 2017: Virology Journal
https://www.readbyqxmd.com/read/28207813/interacting-networks-of-resistance-virulence-and-core-machinery-genes-identified-by-genome-wide-epistasis-analysis
#3
Marcin J Skwark, Nicholas J Croucher, Santeri Puranen, Claire Chewapreecha, Maiju Pesonen, Ying Ying Xu, Paul Turner, Simon R Harris, Stephen B Beres, James M Musser, Julian Parkhill, Stephen D Bentley, Erik Aurell, Jukka Corander
Recent advances in the scale and diversity of population genomic datasets for bacteria now provide the potential for genome-wide patterns of co-evolution to be studied at the resolution of individual bases. Here we describe a new statistical method, genomeDCA, which uses recent advances in computational structural biology to identify the polymorphic loci under the strongest co-evolutionary pressures. We apply genomeDCA to two large population data sets representing the major human pathogens Streptococcus pneumoniae (pneumococcus) and Streptococcus pyogenes (group A Streptococcus)...
February 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28207780/analyzing-pepsin-degradation-assay-conditions-used-for-allergenicity-assessments-to-ensure-that-pepsin-susceptible-and-pepsin-resistant-dietary-proteins-are-distinguishable
#4
Rong Wang, Thomas C Edrington, S Bradley Storrs, Kathleen S Crowley, Jason M Ward, Thomas C Lee, Zi L Liu, Bin Li, Kevin C Glenn
The susceptibility of a dietary protein to proteolytic degradation by digestive enzymes, such as gastric pepsin, provides information on the likelihood of systemic exposure to a structurally intact and biologically active macromolecule, thus informing on the safety of proteins for human and animal consumption. Therefore, the purpose of standardized in vitro degradation studies that are performed during protein safety assessments is to distinguish whether proteins of interest are susceptible or resistant to pepsin degradation via a study design that enables study-to-study comparison...
2017: PloS One
https://www.readbyqxmd.com/read/28205515/tailored-protein-encapsulation-into-a-dna-host-using-geometrically-organized-supramolecular-interactions
#5
Andreas Sprengel, Pascal Lill, Pierre Stegemann, Kenny Bravo-Rodriguez, Elisa-C Schöneweiß, Melisa Merdanovic, Daniel Gudnason, Mikayel Aznauryan, Lisa Gamrad, Stephan Barcikowski, Elsa Sanchez-Garcia, Victoria Birkedal, Christos Gatsogiannis, Michael Ehrmann, Barbara Saccà
The self-organizational properties of DNA have been used to realize synthetic hosts for protein encapsulation. However, current strategies of DNA-protein conjugation still limit true emulation of natural host-guest systems, whose formation relies on non-covalent bonds between geometrically matching interfaces. Here we report one of the largest DNA-protein complexes of semisynthetic origin held in place exclusively by spatially defined supramolecular interactions. Our approach is based on the decoration of the inner surface of a DNA origami hollow structure with multiple ligands converging to their corresponding binding sites on the protein surface with programmable symmetry and range-of-action...
February 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28205050/composite-electrospun-scaffold-derived-from-recombinant-fibroin-of-weaver-ant-oecophylla-smaragdina-as-cell-substratum
#6
Arunrat Khamhaengpol, Sineenat Siri
Unlike silkworm (Bombyx mori) fibroin (SF), weaver ant (Oecophylla smaragdina) fibroin (WAF) is much less studied. Due to differences in amino acid composition and protein structure, this work aimed to produce the recombinant WAF protein, designated as WAF1, and investigated on its potential application as a biomaterial for producing a cell-substratum. The composite electrospun scaffolds derived from poly(vinyl alcohol) (PVA), WAF1, and extracted SF were produced by electrospinning. SEM images revealed non-woven and smooth fibers of PVA, PVA-WAF1, and PVA-SF scaffolds with the average diameters of 204...
February 15, 2017: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/28203478/potential-biochemical-mechanisms-of-lung-injury-in-diabetes
#7
REVIEW
Hong Zheng, Jinzi Wu, Zhen Jin, Liang-Jun Yan
Accumulating evidence has shown that the lung is one of the target organs for microangiopathy in patients with either type 1 or type 2 diabetes mellitus (DM). Diabetes is associated with physiological and structural abnormalities in the diabetic lung concurrent with attenuated lung function. Despite intensive investigations in recent years, the pathogenic mechanisms of diabetic lung injury remain largely elusive. In this review, we summarize currently postulated mechanisms of diabetic lung injury. We mainly focus on the pathogenesis of diabetic lung injury that implicates key pathways, including oxidative stress, non-enzymatic protein glycosylation, polyol pathway, NF-κB pathway, and protein kinase c pathway...
February 2017: Aging and Disease
https://www.readbyqxmd.com/read/28203306/accounting-for-thermodynamic-non-ideality-in-the-guinier-region-of-small-angle-scattering-data-of-proteins
#8
David J Scott
Hydrodynamic studies of the solution properties of proteins and other biological macromolecules are often hard to interpret when the sample is present at a reasonably concentrated solution. The reason for this is that solutions exhibit deviations from ideal behaviour which is manifested as thermodynamic non-ideality. The range of concentrations at which this behaviour typically is exhibited is as low as 1-2 mg/ml, well within the range of concentrations used for their analysis by techniques such as small-angle scattering...
December 2016: Biophysical Reviews
https://www.readbyqxmd.com/read/28202040/subcellular-localization-and-interactions-of-infectious-salmon-anemia-virus-isav-m1-and-nep-as-well-as-host-hsc70
#9
Wenting Zhang, Chengzhi Cai, Li Lin, Yizhi Jane Tao, Meilin Jin
BACKGROUND: Infectious salmon anemia virus (ISAV) is an important fish pathogen that causes high mortality in farmed Atlantic salmon. The ISAV genome consists of eight single-stranded, negative-sense RNA segments. The six largest segments contain one open reading frame (ORF) each, and encode three polymerase proteins, nucleoprotein, fusion protein, and hemagglutinin esterase protein. The two smallest segments contain more than one ORF each. The segment 7 encodes non-structural protein 1 (NS1) and nuclear export protein (NEP), while segment 8 encodes matrix protein 1 and 2 (M1 and M2)...
February 15, 2017: Virology Journal
https://www.readbyqxmd.com/read/28197319/structure-based-design-of-non-natural-peptidic-macrocyclic-mcl-1-inhibitors
#10
Jeffrey W Johannes, Stephanie Bates, Carl Beigie, Matthew A Belmonte, John Breen, Shenggen Cao, Paolo A Centrella, Matthew A Clark, John W Cuozzo, Christoph E Dumelin, Andrew D Ferguson, Sevan Habeshian, David Hargreaves, Camil Joubran, Steven Kazmirski, Anthony D Keefe, Michelle L Lamb, Haiye Lan, Yunxia Li, Hao Ma, Scott Mlynarski, Martin J Packer, Philip B Rawlins, Daniel W Robbins, Haidong Shen, Eric A Sigel, Holly H Soutter, Nancy Su, Dawn M Troast, Haiyun Wang, Kate F Wickson, Chengyan Wu, Ying Zhang, Qiuying Zhao, Xiaolan Zheng, Alexander W Hird
Mcl-1 is a pro-apoptotic BH3 protein family member similar to Bcl-2 and Bcl-xL. Overexpression of Mcl-1 is often seen in various tumors and allows cancer cells to evade apoptosis. Here we report the discovery and optimization of a series of non-natural peptide Mcl-1 inhibitors. Screening of DNA-encoded libraries resulted in hit compound 1, a 1.5 μM Mcl-1 inhibitor. A subsequent crystal structure demonstrated that compound 1 bound to Mcl-1 in a β-turn conformation, such that the two ends of the peptide were close together...
February 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28196397/evolved-distal-tail-carbohydrate-binding-modules-of-lactobacillus-phage-j-1-a-novel-type-of-anti-receptor-widespread-among-lactic-acid-bacteria-phages
#11
Maria-Eugenia Dieterle, Silvia Spinelli, Irina Sadovskaya, Mariana Piuri, Christian Cambillau
Bacteriophage replication requires specific host-recognition. Some siphophages harbour a large complex, the baseplate, at the tip of their non-contractile tail. This baseplate holds receptor binding proteins (RBPs) that can recognize the host cell-wall polysaccharide (CWPS) and specifically attach the phage to its host. While most phages possess a dedicated RBP, the phage J-1 that infects Lactobacillus casei seemed to lack one. We have shown that the phage J-1 distal tail protein (Dit) plays a role in host recognition and that its sequence comprises two inserted modules compared to "classical" Dits...
February 14, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28194788/protein-kinase-a-regulates-c-terminally-truncated-cav-1-2-in-xenopus-oocytes-roles-of-n-and-c-termini-of-the-%C3%AE-1c-subunit
#12
Shimrit Oz, Ines Pankonien, Anouar Belkacemi, Veit Flockerzi, Enno Klussmann, Hannelore Haase, Nathan Dascal
β-Adrenergic stimulation enhances Ca(2+) currents via L-type, voltage-gated CaV 1.2 channels, strengthening cardiac contraction. The signaling via β-adrenergic receptors (β-ARs) involves elevation of cyclic AMP (cAMP) levels and activation of protein kinase A (PKA). However, how PKA affects the channel remains controversial. Recent studies in heterologous systems and genetically engineered mice stress the importance of the posttranslational proteolytic truncation of distal C-terminus (dCT) of the main (α1C ) subunit...
February 14, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28194024/regnase-1-a-rapid-response-ribonuclease-regulating-inflammation-and-stress-responses
#13
REVIEW
Renfang Mao, Riyun Yang, Xia Chen, Edward W Harhaj, Xiaoying Wang, Yihui Fan
RNA-binding proteins (RBPs) are central players in post-transcriptional regulation and immune homeostasis. The ribonuclease and RBP Regnase-1 exerts critical roles in both immune cells and non-immune cells. Its expression is rapidly induced under diverse conditions including microbial infections, treatment with inflammatory cytokines and chemical or mechanical stimulation. Regnase-1 activation is transient and is subject to negative feedback mechanisms including proteasome-mediated degradation or mucosa-associated lymphoid tissue 1 (MALT1) mediated cleavage...
February 13, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28193765/a-novel-chemical-inhibitor-of-aba-signaling-targets-all-aba-receptors
#14
Ya-Jin Ye, Lijuan Zhou, Xue Liu, Hao Liu, Deqiang Li, Minjie Cao, Haifeng Chen, Lin Xu, Jiankang Zhu, Yang Zhao
Abscisic acid (ABA), the most important stress-induced phytohormone, regulates seed dormancy, germination, plant senescence and abiotic stress response. ABA signaling is repressed by protein phosphatases 2C (PP2Cs), then ABA binds to its receptor of the PYR/PYL/RCAR family, which in turn inhibits PP2Cs and activates downstream ABA signaling. The agonist/antagonist of ABA receptors have the potential to unveil the ABA signaling machinery and to become lead compounds for agrochemicals, however, up to now, no broad-spectrum antagonists of ABA receptors blocking all PYR/PYL-PP2C interactions have been identified...
February 13, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28192954/small-emitter-tips-for-native-mass-spectrometry-of-proteins-and-protein-complexes-from-non-volatile-buffers-that-mimic-the-intracellular-environment
#15
Anna Christine Susa, Zijie Xia, Evan R Williams
Salts are often necessary to maintain the native structures and functions of many proteins and protein complexes, but many buffers adversely affect protein analysis by native mass spectrometry (MS). Here, protein and protein complex ions are formed directly from a 150 mM KCl and 25 mM Tris-HCl buffer at pH 7 that is widely used in protein chemistry to mimic the intracellular environment. The protein charge-state distributions are not resolved from electrospray ionization MS using 1.6 μm diameter emitter tips resulting in no mass information...
February 10, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28192432/conformational-diversity-analysis-reveals-three-functional-mechanisms-in-proteins
#16
Alexander Miguel Monzon, Diego Javier Zea, María Silvina Fornasari, Tadeo E Saldaño, Sebastian Fernandez-Alberti, Silvio C E Tosatto, Gustavo Parisi
Protein motions are a key feature to understand biological function. Recently, a large-scale analysis of protein conformational diversity showed a positively skewed distribution with a peak at 0.5 Å C-alpha root-mean-square-deviation (RMSD). To understand this distribution in terms of structure-function relationships, we studied a well curated and large dataset of ~5,000 proteins with experimentally determined conformational diversity. We searched for global behaviour patterns studying how structure-based features change among the available conformer population for each protein...
February 13, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28192157/apaf-1-regulation-and-function-in-cell-death
#17
REVIEW
Raheleh Shakeri, Asma Kheirollahi, Jamshid Davoodi
Apoptosis, a form of programmed cell death, is responsible for eliminating damaged or unnecessary cells in multicellular organisms. Various types of intracellular stress trigger apoptosis by induction of cytochrome c release from mitochondria into the cytosol. Apoptotic protease activating factor-1 (Apaf-1) is a key molecule in the intrinsic or mitochondrial pathway of apoptosis, which oligomerizes in response to cytochrome c release and forms a large complex known as apoptosome. Procaspase-9, an initiator caspase in the mitochondrial pathway, is recruited and activated by the apoptosome leading to downstream caspase-3 processing...
February 9, 2017: Biochimie
https://www.readbyqxmd.com/read/28191590/calcium-binding-ability-of-recombinant-buffalo-regucalcin-a-study-using-circular-dichroism-spectroscopy
#18
P Harikrishna, Jobin Thomas, A M Shende, S K Bhure
Regucalcin is a calcium regulating multifunctional protein reported to have many important functions like calcium homeostasis, anti-oxidative, anti-apoptotic and anti-cancerous functions. Although it is demonstrated as a calcium regulating protein, the calcium binding ability of regucalcin is still a controversy. The main reason for the controversy is that it lacks a typical EF hand motif which is common to most of the calcium binding proteins. Even though many studies reported regucalcin as a calcium binding protein, there are some studies reporting regucalcin as non-calcium binding also...
February 13, 2017: Protein Journal
https://www.readbyqxmd.com/read/28188780/structural-insights-into-the-cold-adaptation-of-the-photosynthetic-pigment-protein-c-phycocyanin-from-an-arctic-cyanobacterium
#19
Hai-Nan Su, Qian-Min Wang, Chun-Yang Li, Kang Li, Wei Luo, Bo Chen, Xi-Ying Zhang, Qi-Long Qin, Bai-Cheng Zhou, Xiu-Lan Chen, Yu-Zhong Zhang, Bin-Bin Xie
The cold adaptation mechanism of phycobiliproteins, the major photosynthetic pigment-proteins in cyanobacteria and red algae, has rarely been studied. Here we reported the biochemical, structural, and molecular dynamics simulation study of the C-phycocyanin from Arctic cyanobacterial strain Pseudanabaena sp. LW0831. We characterized the phycobilisome components of LW0831 and obtained their gene sequences. Compared to the mesophilic counterpart from Arthrospira platensis (Ar-C-PC), LW0831 C-phycocyanin (Ps-C-PC) has a decreased thermostability (∆Tm of -16°C), one of the typical features of cold-adapted enzymes...
February 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28187312/glucose-phosphorylated-on-carbon-6-suppresses-lipopolysaccharide-binding-to-lipopolysaccharide-binding-protein-and-inhibits-its-bioactivities
#20
Yuu Fujita, Kiyohito Yagi
Lipid A comprises the active region of lipopolysaccharide (LPS), and its phosphate group is required for LPS activities. Additionally, it is essential for effects of inhibitors of LPS-induced coagulation activity in limulus amebocyte lysate (LAL) tests. Lipid A has phosphorylated glucosamine residues, which are structurally similar to glucose 1-phosphate (G1P) and glucose 6-phosphate (G6P). This study focused on the antagonistic effects of glucose phosphates on the action of protein or non-protein inhibitors against LAL coagulation, LPS-LPS-binding protein (LBP) interaction, and LPS bioactivities...
February 6, 2017: International Immunopharmacology
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