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Non structural protein 3

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https://www.readbyqxmd.com/read/28238947/identification-of-novel-mrp3-inhibitors-based-on-computational-models-and-validation-using-an-in-vitro-membrane-vesicle-assay
#1
Izna Ali, Matthew A Welch, Yang Lu, Peter W Swaan, Kim L R Brouwer
INTRODUCTION: Multidrug resistance-associated protein 3 (MRP3), an efflux transporter on the hepatic basolateral membrane, may function as a compensatory mechanism to prevent the accumulation of anionic substrates (e.g., bile acids) in hepatocytes. Inhibition of MRP3 may disrupt bile acid homeostasis and is one hypothesized risk factor for the development of drug-induced liver injury (DILI). Therefore, identifying potential MRP3 inhibitors could help mitigate the occurrence of DILI. METHODS: Bayesian models were developed using MRP3 transporter inhibition data for 86 structurally diverse drugs...
February 23, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28238818/the-conformation-of-human-phospholipid-scramblase-1-as-studied-by-infrared-spectroscopy-effects-of-calcium-and-detergent
#2
Nagore Andraka, Lissete Sánchez-Magraner, Marcos García-Pacios, Félix M Goñi, José L R Arrondo
Human phospholipid scramblase 1 (SCR) is a membrane protein that catalyzes the transmembrane (flip-flop) motion of phospholipids. It can also exist in a non membrane-bound form in the nucleus, where it modulates several aspects of gene expression. Catalysis of phospholipid flip-flop requires the presence of millimolar Ca(2+), and occurs in the absence of ATP. Membrane-bound SCR contains a C-terminal α-helical domain embedded in the membrane bilayer. The latter domain can be removed giving rise to a stable truncated mutant SCRΔ that is devoid of scramblase activity...
February 23, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28238661/motor-activity-dependent-and-independent-functions-of-myosin-ii-contribute-to-actomyosin-ring-assembly-and-contraction-in-schizosaccharomyces-pombe
#3
Saravanan Palani, Ting Gang Chew, Srinivasan Ramanujam, Anton Kamnev, Shrikant Harne, Bernardo Chapa-Y-Lazo, Rebecca Hogg, Mayalagu Sevugan, Mithilesh Mishra, Pananghat Gayathri, Mohan K Balasubramanian
Cytokinesis depends on a contractile actomyosin ring in many eukaryotes [1-3]. Myosin II is a key component of the actomyosin ring, although whether it functions as a motor or as an actin cross-linker to exert its essential role is disputed [1, 4, 5]. In Schizosaccharomyces pombe, the myo2-E1 mutation affects the upper 50 kDa sub-domain of the myosin II heavy chain, and cells carrying this lethal mutation are defective in actomyosin ring assembly at the non-permissive temperature [6, 7]. myo2-E1 also affects actomyosin ring contraction when rings isolated from permissive temperature-grown cells are incubated with ATP [8]...
February 21, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28235481/molecular-determinants-of-the-olfactory-receptor-olfr544-activation-by-azelaic-acid
#4
Trung Thanh Thach, Yu-Jung Hong, Sangho Lee, Sung-Joon Lee
The mouse olfactory receptor Olfr544 is expressed in several non-olfactory tissues and has been suggested as a functional receptor regulating different signaling pathways. However, the molecular interaction between Olfr544 and its natural ligand, azelaic acid (AzA), remains poorly characterized, primarily due to difficulties in the heterologous expression of the receptor protein on the cell membrane and lack of entire protein structure. In this report, we describe the molecular determinants of Olfr544 activation by AzA...
February 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28230822/disordered-redox-metabolism-of-brain-cells-in-rats-exposed-to-low-doses-of-ionizing-radiation-or-uhf-electromagnetic-radiation
#5
A P Burlaka, M O Druzhyna, A V Vovk, S М Lukin
AIM: To investigate the changes of redox-state of mammalian brain cells as the critical factor of initiation and formation of radiation damage of biological structures in setting of continuous exposure to low doses of ionizing radiation or fractionated ultra high frequency electromagnetic radiation (UHF EMR) at non-thermal levels. MATERIALS AND METHODS: The influence of low-intensity ionizing radiation was studied on outbred female rats kept for 1.5 years in the Chernobyl accident zone...
December 2016: Experimental Oncology
https://www.readbyqxmd.com/read/28229898/histomorphometric-characterization-of-subgemmal-neurogenous-plaques
#6
Ana Carolina Amorim Pellicioli, Felipe Paiva Fonseca, Rodrigo Neves Silva, Luiz Alcino Monteiro Gueiros, Oslei Paes de Almeida, Pablo Agustin Vargas, Marcio Ajudarte Lopes, Helder Antonio Rebelo Pontes, Manoela Domingues Martins, Vinícius Coelho Carrard, Alan Roger Santos-Silva
OBJECTIVES: The aim of this study was to characterize the histomorphometric features of subgemmal neurogenous plaques (SNPs) to better understand their relationship to surrounding microanatomy included in the tissue biopsy samples of the tongue. STUDY DESIGN: A 12-year retrospective study on the files of 3 oral pathology centers yielded 28 SNPs. Hematoxylin and eosin-stained sections were used for histologic analysis, and immunohistochemical staining for S100 protein was performed to better characterize the neural structures...
January 9, 2017: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
https://www.readbyqxmd.com/read/28225828/systematic-analysis-of-non-structural-protein-features-for-the-prediction-of-ptm-function-potential-by-artificial-neural-networks
#7
Henry M Dewhurst, Matthew P Torres
Post-translational modifications (PTMs) provide an extensible framework for regulation of protein behavior beyond the diversity represented within the genome alone. While the rate of identification of PTMs has rapidly increased in recent years, our knowledge of PTM functionality encompasses less than 5% of this data. We previously developed SAPH-ire (Structural Analysis of PTM Hotspots) for the prioritization of eukaryotic PTMs based on function potential of discrete modified alignment positions (MAPs) in a set of 8 protein families...
2017: PloS One
https://www.readbyqxmd.com/read/28225020/improved-antitumor-activity-of-trail-fusion-protein-via-formation-of-self-assembling-nanoparticle
#8
Kaizong Huang, Ningjun Duan, Chunmei Zhang, Ran Mo, Zichun Hua
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been known as a promising agent for cancer therapy due to its specific apoptosis-inducing effect on tumor cells rather than most normal cells. However, systemically delivered TRAIL suffers from a rapid clearance from the body with an extremely short half-life. Thermally responsive elastin-like polypeptides (ELPs) are a promising class of temperature sensitive biopolymers based on the structural motif found in mammalian tropoelastin and retain the advantages of polymeric drug delivery systems...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28219079/light-induced-structural-changes-and-the-site-of-o-o-bond-formation-in-psii-caught-by-xfel
#9
Michihiro Suga, Fusamichi Akita, Michihiro Sugahara, Minoru Kubo, Yoshiki Nakajima, Takanori Nakane, Keitaro Yamashita, Yasufumi Umena, Makoto Nakabayashi, Takahiro Yamane, Takamitsu Nakano, Mamoru Suzuki, Tetsuya Masuda, Shigeyuki Inoue, Tetsunari Kimura, Takashi Nomura, Shinichiro Yonekura, Long-Jiang Yu, Tomohiro Sakamoto, Taiki Motomura, Jing-Hua Chen, Yuki Kato, Takumi Noguchi, Kensuke Tono, Yasumasa Joti, Takashi Kameshima, Takaki Hatsui, Eriko Nango, Rie Tanaka, Hisashi Naitow, Yoshinori Matsuura, Ayumi Yamashita, Masaki Yamamoto, Osamu Nureki, Makina Yabashi, Tetsuya Ishikawa, So Iwata, Jian-Ren Shen
Photosystem II (PSII) is a huge membrane-protein complex consisting of 20 different subunits with a total molecular mass of 350 kDa for a monomer. It catalyses light-driven water oxidation at its catalytic centre, the oxygen-evolving complex (OEC). The structure of PSII has been analysed at 1.9 Å resolution by synchrotron radiation X-rays, which revealed that the OEC is a Mn4CaO5 cluster organized in an asymmetric, 'distorted-chair' form. This structure was further analysed with femtosecond X-ray free electron lasers (XFEL), providing the 'radiation damage-free' structure...
February 20, 2017: Nature
https://www.readbyqxmd.com/read/28214373/improved-detection-of-zika-virus-rna-in-human-and-animal-specimens-by-a-novel-highly-sensitive-and-specific-real-time-rt-pcr-assay-targeting-the-5-untranslated-region-of-zika-virus
#10
Jasper Fuk-Woo Chan, Cyril Chik-Yan Yip, Kah-Meng Tee, Zheng Zhu, Jessica Oi-Ling Tsang, Kenn Ka-Heng Chik, Terance Gi-Wai Tsang, Chris Chung-Sing Chan, Vincent Kwok-Man Poon, Siddharth Sridhar, Feifei Yin, Ivan Fan-Ngai Hung, Sandy Ka-Yee Chau, Anna Jinxia Zhang, Kwok-Hung Chan, Kwok-Yung Yuen
OBJECTIVE AND METHOD: We developed and evaluated five novel real-time RT-PCR assays targeting conserved regions in the 5'-untranslated region (5'-UTR), envelope (E'), non-structural protein 2A (NS2A), NS5, and 3'-UTR of the ZIKV genome. RESULTS: The ZIKV-5'-UTR assay exhibited the lowest in-vitro limit of detection (5-10 RNA copies/reaction and 3.0×10(-1) plaque-forming units/ml). Compared to the modified version of a widely adopted RT-PCR assay targeting the ZIKV-E gene, the ZIKV-5'-UTR assay showed better sensitivity in human clinical specimens, and representative mouse specimens, including many organs which are known to be involved in human ZIKV infection but difficult to obtain in clinical settings...
February 18, 2017: Tropical Medicine & International Health: TM & IH
https://www.readbyqxmd.com/read/28208577/single-nucleotide-polymorphism-of-ppar%C3%AE-a-protein-at-the-crossroads-of-physiological-and-pathological-processes
#11
Maria Petrosino, Laura Lori, Alessandra Pasquo, Clorinda Lori, Valerio Consalvi, Velia Minicozzi, Silvia Morante, Antonio Laghezza, Alessandra Giorgi, Davide Capelli, Roberta Chiaraluce
Genome polymorphisms are responsible for phenotypic differences between humans and for individual susceptibility to genetic diseases and therapeutic responses. Non-synonymous single-nucleotide polymorphisms (nsSNPs) lead to protein variants with a change in the amino acid sequence that may affect the structure and/or function of the protein and may be utilized as efficient structural and functional markers of association to complex diseases. This study is focused on nsSNP variants of the ligand binding domain of PPARγ a nuclear receptor in the superfamily of ligand inducible transcription factors that play an important role in regulating lipid metabolism and in several processes ranging from cellular differentiation and development to carcinogenesis...
February 10, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28208060/rna-toxicity-and-foci-formation-in-microsatellite-expansion-diseases
#12
REVIEW
Nan Zhang, Tetsuo Ashizawa
More than 30 incurable neurological and neuromuscular diseases are caused by simple microsatellite expansions consisted of 3-6 nucleotides. These repeats can occur in non-coding regions and often result in a dominantly inherited disease phenotype that is characteristic of a toxic RNA gain-of-function. The expanded RNA adopts unusual secondary structures, sequesters various RNA binding proteins to form insoluble nuclear foci, and causes cellular defects at a multisystem level. Nuclear foci are dynamic in size, shape and colocalization of RNA binding proteins in different expansion diseases and tissue types...
February 13, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/28202596/the-3-hydroxyacyl-acp-dehydratase-component-of-the-plant-mitochondrial-fatty-acid-synthase-system
#13
Xin Guan, Yozo Okazaki, Andrew Lithio, Ling Li, Xuefeng Zhao, Huanan Jin, Dan Nettleton, Kazuki Saito, Basil J Nikolau
We report the characterization of the Arabidopsis 3-hydroxyacyl-acyl carrier protein (ACP) dehydratase (mtHD) component of the mitochondrial fatty acid synthase (mtFAS) system, encoded by AT5G60335. The mitochondrial localization and catalytic capability of mtHD were demonstrated with a green fluorescent protein (GFP) transgenesis experiment, and by in vivo complementation and in vitro enzymatic assays. RNAi knockdown lines with reduced mtHD expression exhibit traits typically associated with mtFAS mutants, namely a miniaturized morphological appearance, reduced lipoylation of lipoylated proteins, and altered metabolomes consistent with the reduced catalytic activity of lipoylated enzymes...
February 15, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28202376/structural-features-of-zika-virus-non-structural-proteins-3-and-5-and-its-individual-domains-in-solution-as-well-as-insights-into-ns3-inhibition
#14
Wuan Geok Saw, Ankita Pan, Malathy Sony Subramanian Manimekalai, Gerhard Grüber
Zika virus (ZIKV) has emerged as a pathogen of major health concern. The virus relies on its non-structural protein 5 (NS5) including a methyl-transferase (MTase) and a RNA-dependent RNA polymerase (RdRp) for capping and synthesis of the viral RNA and the nonstructural protein 3 (NS3) with its protease and helicase domain for polyprotein possessing, unwinding dsRNA proceeding replication, and NTPase/RTPase activities. In this study we present for the first time insights into the overall structure of the entire French Polynesia ZIKV NS3 in solution...
February 12, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28198987/the-content-of-mucin-muc-2-3-and-4-antigens-in-the-bronchial-mucosa-membrane-of-chronic-obstructive-pulmonary-disease-patients-during-acute-exacerbation-initial-report
#15
Svetlana Kovalenko, Andrey Dorofieiev
INTRODUCTION: Changes in mucin production and dyscrinia are common features of inflammation in chronic obstructive pulmonary disease (COPD). Immunohistochemical assessment of MUC-2, MUC-3, MUC-4 expression in the integumentary epithelium, goblet cells, the epithelium of mucous glands and stroma fusiform cells of the bronchial mucosa of COPD patients during an infectious and noninfectious exacerbation was performed. MATERIAL AND METHODS: 30 patients with stage III COPD were enrolled to the study...
2017: Adv Respir Med
https://www.readbyqxmd.com/read/28197319/structure-based-design-of-non-natural-peptidic-macrocyclic-mcl-1-inhibitors
#16
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/28192432/conformational-diversity-analysis-reveals-three-functional-mechanisms-in-proteins
#17
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
#18
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
#19
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
#20
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...
April 2017: Biochimica et Biophysica Acta
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