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Non structural protein 3

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https://www.readbyqxmd.com/read/28345935/targeting-self-binding-peptides-as-a-novel-strategy-to-regulate-protein-activity-and-function-a-case-study-on-the-proto-oncogene-tyrosine-protein-kinase-c-src
#1
Zhengya Bai, Shasha Hou, Shilei Zhang, Zhongyan Li, Peng Zhou
Previously, we have reported a new biomolecular phenomenon spanning between protein folding and binding, termed as self-binding peptides (SBPs), where a short peptide segment in monomeric protein functions as molecular switch by dynamically binding to/unbinding from its cognate domain in the monomer (Yang C, Zhang S, He P, Wang C, Huang J, Zhou P. Self-binding peptides: folding or binding? J. Chem. Inf. MODEL: 2015, 55: 329-342). Here, we attempt to raise the SBP as a new class of druggable targets to regulate the biological activity and function of proteins...
March 27, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28344334/the-kif1a-homolog-unc-104-is-important-for-spontaneous-release-postsynaptic-density-maturation-and-perisynaptic-scaffold-organization
#2
Yao V Zhang, Shabab B Hannan, Jeannine V Kern, Doychin T Stanchev, Baran Koç, Thomas R Jahn, Tobias M Rasse
The kinesin-3 family member KIF1A has been shown to be important for experience dependent neuroplasticity. In Drosophila, amorphic mutations in the KIF1A homolog unc-104 disrupt the formation of mature boutons. Disease associated KIF1A mutations have been associated with motor and sensory dysfunctions as well as non-syndromic intellectual disability in humans. A hypomorphic mutation in the forkhead-associated domain of Unc-104, unc-104(bris), impairs active zone maturation resulting in an increased fraction of post-synaptic glutamate receptor fields that lack the active zone scaffolding protein Bruchpilot...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28334870/annealing-helicase-harp-closes-rpa-stabilized-dna-bubbles-non-processively
#3
Daniel R Burnham, Bas Nijholt, Iwijn De Vlaminck, Jinhua Quan, Timur Yusufzai, Cees Dekker
We investigate the mechanistic nature of the Snf2 family protein HARP, mutations of which are responsible for Schimke immuno-osseous dysplasia. Using a single-molecule magnetic tweezers assay, we construct RPA-stabilized DNA bubbles within torsionally constrained DNA to investigate the annealing action of HARP on a physiologically relevant substrate. We find that HARP closes RPA-stabilized bubbles in a slow reaction, taking on the order of tens of minutes for ∼600 bp of DNA to be re-annealed. The data indicate that DNA re-anneals through the removal of RPA, which is observed as clear steps in the bubble-closing traces...
February 28, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334742/recognition-but-no-repair-of-abasic-site-in-single-stranded-dna-by-human-ribosomal-us3-protein-residing-within-intact-40s-subunit
#4
Anastasia S Grosheva, Dmitry O Zharkov, Joachim Stahl, Alexander V Gopanenko, Alexey E Tupikin, Marsel R Kabilov, Dmitri M Graifer, Galina G Karpova
Isolated human ribosomal protein uS3 has extra-ribosomal functions including those related to base excision DNA repair, e.g. AP lyase activity that nicks double-stranded (ds) DNA 3΄ to the abasic (AP) site. However, the ability of uS3 residing within ribosome to recognize and cleave damaged DNA has never been addressed. Here, we compare interactions of single-stranded (ss) DNA and dsDNA bearing AP site with human ribosome-bound uS3 and with the isolated protein, whose interactions with ssDNA were not yet studied...
January 30, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28326775/determining-cysteines-available-for-covalent-inhibition-across-the-human-kinome
#5
Zheng Zhao, Qingsong Liu, Spencer Bliven, Lei Xie, Philip E Bourne
Covalently bound protein kinase inhibitors have been frequently designed to target non-catalytic cysteines at the ATP binding site. Thus, it is important to know if a given cysteine can form a covalent bond. Here we combine a function-site interaction fingerprint method and DFT calculations to determine the potential of cysteines to form a covalent interaction with an inhibitor. By harnessing the human structural kinome, a comprehensive structure-based binding site cysteine dataset was assembled. The orientation of the cysteine thiol group indicates which cysteines can potentially form covalent bonds...
March 22, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28322030/melatonin-and-il-25-modulate-apoptosis-and-angiogenesis-mediators-in-metastatic-cf-41-and-non-metastatic-cmt-u229-canine-mammary-tumour-cells
#6
G B Gelaleti, T F Borin, L B Maschio-Signorini, M G Moschetta, E Hellmén, A M Viloria-Petit, D A P C Zuccari
BACKGROUND: Melatonin has oncostatic actions and IL-25 is active in inflammatory processes that induce apoptosis in tumor cells AIM: The aim of this study was to evaluate melatonin and IL-25 in metastatic (CF-41) and non-metastatic (CMT-U229) canine mammary tumor cells cultured as monolayers and tridimensional structures. MATERIALS AND METHODS: The cells were treated with melatonin, IL-25 and IL-17B silencing gene and performed cell viability, gene and protein expression of caspase-3 and VEGFA (Vascular endothelial growth factor A) and an apoptosis membrane protein array...
March 20, 2017: Veterinary and Comparative Oncology
https://www.readbyqxmd.com/read/28321286/crispr-cas9-mediated-heterozygous-knockout-of-the-autism-gene-chd8-and-characterization-of-its-transcriptional-networks-in-cerebral-organoids-derived-from-ips-cells
#7
Ping Wang, Ryan Mokhtari, Erika Pedrosa, Michael Kirschenbaum, Can Bayrak, Deyou Zheng, Herbert M Lachman
BACKGROUND: CHD8 (chromodomain helicase DNA-binding protein 8), which codes for a member of the CHD family of ATP-dependent chromatin-remodeling factors, is one of the most commonly mutated genes in autism spectrum disorders (ASD) identified in exome-sequencing studies. Loss of function mutations in the gene have also been found in schizophrenia (SZ) and intellectual disabilities and influence cancer cell proliferation. We previously reported an RNA-seq analysis carried out on neural progenitor cells (NPCs) and monolayer neurons derived from induced pluripotent stem (iPS) cells that were heterozygous for CHD8 knockout (KO) alleles generated using CRISPR-Cas9 gene editing...
2017: Molecular Autism
https://www.readbyqxmd.com/read/28320876/taking-a-step-back-from-back-translocation-an-integrative-view-of-lepa-ef4-s-cellular-function
#8
Jalyce L E Heller, Rajashekhar Kamalampeta, Hans-Joachim Wieden
Protein synthesis, the translation of mRNA into a polypeptide facilitated by the ribosome, is assisted by a variety of protein factors, some of which are GTPases. In addition to four highly conserved and well-understood GTPases with known function, there are also a number of non-canonical GTPases that are implicated in translation but whose functions are not fully understood. LepA/EF4 is one of these non-canonical GTPases. It is highly conserved and present in bacteria, mitochondria and chloroplasts, but its functional role in the cell remains unknown...
March 20, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28299939/kilobase-pair-chromatin-fiber-contacts-promoted-by-living-system-like-dna-linker-length-distributions-and-nucleosome-depletion
#9
Gavin D Bascom, Taejin Kim, Tamar Schlick
While genome-wide chromosomal contact maps are available for a wide range of cell lines, fiber configurations on the kilobase (kb) chromatin level are largely unknown. Of particular interest is to understand how long-range contacts form and are related to gene regulation. It is believed that nucleosome placement, or linker-length patterns, in chromatin have evolved to yield specific spatial features in chromatin fibers. Here we examine by mesoscale model- ing how such long-range contacts and looping depend on DNA linker length values between successive nucleosomes...
March 16, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28299648/structure-and-biophysics-of-cbf%C3%AE-runx-and-its-translocation-products
#10
Tahir H Tahirov, John Bushweller
The core binding factor (CBF) transcription factor is somewhat unique in that it is composed of a DNA binding RUNX subunit (RUNX1, 2, or 3) and a non-DNA binding CBFβ subunit, which modulates RUNX protein activity by modulating the auto-inhibition of the RUNX subunits. Since the discovery of this fascinating transcription factor more than 20 years ago, there has been a robust effort to characterize the structure as well as the biochemical properties of CBF. More recently, these efforts have also extended to the fusion proteins that arise from the subunits of CBF in leukemia...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28298598/proteolytic-cleavage-of-bovine-adenovirus-3-encoded-pviii
#11
Amit Gaba, Lisanework Ayalew, Niraj Makadiya, Suresh Tikoo
Proteolytic maturation involving cleavage of one non-structural and six structural precursor proteins including pVIII by adenovirus protease is an important aspect of adenovirus life cycle. The pVIII encoded by BAdV-3 is a protein of 216 amino acids, which contains two potential protease cleavage sites. Here, we report that BAdV-3 pVIII is cleaved by adenovirus protease at both potential consensus protease cleavage sites. Usage of at least one cleavage site appears essential for the production of progeny BAdV-3 virions as glycine to alanine mutation of both protease cleavage sites appears lethal for the production of progeny virions...
March 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28290509/an-outbreak-of-severe-infections-among-australian-infants-caused-by-a-novel-recombinant-strain-of-human-parechovirus-type-3
#12
Tiffanie M Nelson, Peter Vuillermin, Jason Hodge, Julian Druce, David T Williams, Rekha Jasrotia, Soren Alexandersen
Human parechovirus types 1-16 (HPeV1-16) are positive strand RNA viruses in the family Picornaviridae. We investigated a 2015 outbreak of HPeV3 causing illness in infants in Victoria, Australia. Virus genome was extracted from clinical material and isolates and sequenced using a combination of next generation and Sanger sequencing. The HPeV3 outbreak genome was 98.7% similar to the HPeV3 Yamagata 2011 lineage for the region encoding the structural proteins up to nucleotide position 3115, but downstream of that the genome varied from known HPeV sequences with a similarity of 85% or less...
March 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28289947/in-vivo-and-in-vitro-identification-of-endocannabinoid-signaling-in-periodontal-tissues-and-their-potential-role-in-local-pathophysiology
#13
Anna Konermann, Andreas Jäger, Stefanie A E Held, P Brossart, Anne Schmöle
The endocannabinoid system (ECS) with its binding receptors CB1 and CB2 impacts multiple pathophysiologies not only limited to neuronal psychoactivity. CB1 is assigned to cerebral neuron action, whereas CB2 is mainly expressed in different non-neuronal tissues and associated with immunosuppressive effects. Based on these tissue-selective CB receptor roles, it was the aim of this study to analyze potential expression in periodontal tissues under physiological conditions and inflammatory states. In vivo, CB receptor expression was investigated on human periodontal biopsies with or without bacterial inflammation and on rat maxillae with or without sterile inflammation...
March 14, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28287470/the-application-of-curve-fitting-on-the-voltammograms-of-various-isoforms-of-metallothioneins-metal-complexes
#14
Miguel Angel Merlos Rodrigo, Jorge Molina-López, Ana Maria Jimenez Jimenez, Elena Planells Del Pozo, Pavlina Adam, Tomas Eckschlager, Ondrej Zitka, Lukas Richtera, Vojtech Adam
The translation of metallothioneins (MTs) is one of the defense strategies by which organisms protect themselves from metal-induced toxicity. MTs belong to a family of proteins comprising MT-1, MT-2, MT-3, and MT-4 classes, with multiple isoforms within each class. The main aim of this study was to determine the behavior of MT in dependence on various externally modelled environments, using electrochemistry. In our study, the mass distribution of MTs was characterized using MALDI-TOF. After that, adsorptive transfer stripping technique with differential pulse voltammetry was selected for optimization of electrochemical detection of MTs with regard to accumulation time and pH effects...
March 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28285997/ccm-3-promotes-c-%C3%A2-elegans-germline-development-by-regulating-vesicle-trafficking-cytokinesis-and-polarity
#15
Swati Pal, Benjamin Lant, Bin Yu, Ruilin Tian, Jiefei Tong, Jonathan R Krieger, Michael F Moran, Anne-Claude Gingras, W Brent Derry
Cerebral cavernous malformations (CCMs) are vascular defects of the CNS that arise from loss of integrity of the endothelial cells lining blood capillaries, causing leakage of blood into the brain [1]. This results in headaches, seizures, and/or hemorrhagic stroke, depending on the location of the lesion. CCM affects 0.5% of the population and follows an autosomal dominant inheritance pattern caused by mutations in one of the three genes: CCM1 (gene name KRIT1), CCM2 (also known as malcavernin or OSM), and CCM3 (gene name PDCD10) [2, 3], with the earliest onset and most severe prognosis occurring in CCM3 patients [4]...
March 20, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28284855/identification-expression-pattern-and-feature-analysis-of-cuticular-protein-genes-in-the-pine-moth-dendrolimus-punctatus-lepidoptera-lasiocampidae
#16
Cong-Hui Yang, Peng-Cheng Yang, Su-Fang Zhang, Zhi-Yong Shi, Le Kang, Ai-Bing Zhang
Cuticular proteins (CPs) are vital components of the insects' cuticle that support movement and protect insect from adverse environmental conditions. The CPs exist in a large number and diversiform structures, thus, the accurate annotation is the first step to interpreting their roles in insect growth. The rapid development of sequencing technology has simplified the access to the information on protein sequences, especially for non-model species. Dendrolimus punctatus is a Lepidopteran defoliator, and its periodic outbreaks cause severe damage to the coniferous forests...
March 9, 2017: Insect Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28282625/phosphorylation-of-the-regulatory-domain-of-human-tyrosine-hydroxylase-1-monitored-using-non-uniformly-sampled-nmr
#17
Petr Louša, Hana Nedozrálová, Erik Župa, Jiří Nováček, Jozef Hritz
Human tyrosine hydroxylase 1 (hTH1) activity is regulated by phosphorylation of its regulatory domain (RD-hTH1) and by an interaction with the 14-3-3 protein. The RD-hTH1 is composed of a structured region (66-169) preceded by an intrinsically disordered protein region (IDP, hTH1_65) containing two phosphorylation sites (S19 and S40) which are highly relevant for its increase in activity. The NMR signals of the IDP region in the non-phosphorylated, singly phosphorylated (pS40) and doubly phosphorylated states (pS19_pS40) were assigned by non-uniformly sampled spectra with increased dimensionality (5D)...
January 27, 2017: Biophysical Chemistry
https://www.readbyqxmd.com/read/28276482/multimer-recognition-and-secretion-by-the-non-classical-secretion-pathway-in-bacillus-subtilis
#18
Liuqun Zhao, Jingqi Chen, Jibin Sun, Dawei Zhang
Non-classical protein secretion in bacteria is a common phenomenon. However, the selection principle for non-classical secretion pathways remains unclear. Here, our experimental data, to our knowledge, are the first to show that folded multimeric proteins can be recognized and excreted by a non-classical secretion pathway in Bacillus subtilis. We explored the secretion pattern of a typical cytoplasmic protein D-psicose 3-epimerase from Ruminococcus sp. 5_1_39BFAA (RDPE), and showed that its non-classical secretion is not simply due to cell lysis...
March 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28259941/consumption-of-policosanol-enhances-hdl-functionality-via-cetp-inhibition-and-reduces-blood-pressure-and-visceral-fat-in-young-and-middle-aged-subjects
#19
Jae-Yong Kim, Seong-Min Kim, Suk-Jeong Kim, Eun-Young Lee, Jae-Ryong Kim, Kyung-Hyun Cho
It is well-known that policosanol can improve serum lipid profiles, although the physiological mechanism is still unknown. Here, we investigated functional and structural changes in lipoproteins after consumption of policosanol. To investigate the physiological effect of policosanol, we analyzed serum parameters in young non-smoker (YN; n=7, 24.0±2.4 years), young smoker (YS; n=7, 26.3±1.5 years), and middle-aged subjects (MN; n=11, 52.5±9.8 years) who consumed policosanol daily (10 mg/day) for 8 weeks...
February 24, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28259528/structural-insights-of-smkdac8-inhibitors-targeting-schistosoma-epigenetics-through-a-combined-structure-based-3d-qsar-in-vitro-and-synthesis-strategy
#20
Flavio Ballante, D Rajasekhar Reddy, Nancy J Zhou, Garland R Marshall
A predictive structure-based 3D QSAR (COMBINEr 2.0) model of the Schistosoma mansoni lysine deacetylase 8 enzyme (SmKDAC8) was developed, validated and used to perform virtual screening (VS) of the NCI Diversity Set V database (1593 compounds). Three external datasets (with congeneric structures to those experimentally resolved in complexes by X-ray and previously reported as SmKDAC8 inhibitors) were employed to compose and validate the most predictive model. Two series characterized by 104 benzodiazepine derivatives (BZDs) and 60 simplified largazole analogs (SLAs), recently reported by our group as human KDAC inhibitors, were tested for their inhibition potency against SmKDAC8 to probe the predictive capability of the quantitative models against compounds with diverse structures...
February 13, 2017: Bioorganic & Medicinal Chemistry
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