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https://www.readbyqxmd.com/read/28231526/enhanced-identification-of-%C3%AE-lactamases-and-its-classes-using-sequence-physicochemical-and-evolutionary-information-with-sequence-feature-characterization-of-the-classes
#1
Abhigyan Nath, S Karthikeyan
β-lactamases provides one of the most successful means of evading the therapeutic effects of β lactam class of antibiotics by many gram positive and gram negative bacteria. On the basis of sequence identity, β-lactamases have been identified into four distinct classes- A, B, C and D. The classes A, C and D are the serine β-lactamases and class B is the metallo-lactamse. In the present study, we developed a two stage cascade classification system. The first-stage performs the classification of β-lactamases from non-β-lactamases and the second-stage performs the further classification of β-lactamases into four different β-lactamase classes...
February 14, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28230860/carma2sh-and-ulk2-control-pathogen-associated-molecular-patterns-recognition-in-human-keratinocytes-psoriasis-linked-carma2sh-mutants-escape-ulk2-censorship
#2
Ivan Scudiero, Pellegrino Mazzone, Luca E D'Andrea, Angela Ferravante, Tiziana Zotti, Gianluca Telesio, Gabriele De Rubis, Carla Reale, Maddalena Pizzulo, Shanmugakonar Muralitharan, Pasquale Vito, Romania Stilo
The molecular complexes formed by specific members of the family of CARMA proteins, the CARD domain-containing adapter molecule BCL10 and MALT1 (CBM complex) represent a central hub in regulating activation of the pleiotropic transcription factor NF-κB. Recently, missense mutations in CARMA2sh have been shown to cause psoriasis in a dominant manner and with high penetrancy. Here, we demonstrate that in human keratinocytes CARMA2sh plays an essential role in the signal transduction pathway that connects pathogen-associated molecular patterns recognition to NF-κB activation...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28230857/protein-phosphatase-4-coordinates-glial-membrane-recruitment-and-phagocytic-clearance-of-degenerating-axons-in-drosophila
#3
Lilly M Winfree, Sean D Speese, Mary A Logan
Neuronal damage induced by injury, stroke, or neurodegenerative disease elicits swift immune responses from glial cells, including altered gene expression, directed migration to injury sites, and glial clearance of damaged neurons through phagocytic engulfment. Collectively, these responses hinder further cellular damage, but the mechanisms that underlie these important protective glial reactions are still unclear. Here, we show that the evolutionarily conserved trimeric protein phosphatase 4 (PP4) serine/threonine phosphatase complex is a novel set of factors required for proper glial responses to nerve injury in the adult Drosophila brain...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28230762/the-development-of-ck2-inhibitors-from-traditional-pharmacology-to-in-silico-rational-drug-design
#4
REVIEW
Giorgio Cozza
Casein kinase II (CK2) is an ubiquitous and pleiotropic serine/threonine protein kinase able to phosphorylate hundreds of substrates. Being implicated in several human diseases, from neurodegeneration to cancer, the biological roles of CK2 have been intensively studied. Upregulation of CK2 has been shown to be critical to tumor progression, making this kinase an attractive target for cancer therapy. Several CK2 inhibitors have been developed so far, the first being discovered by "trial and error testing". In the last decade, the development of in silico rational drug design has prompted the discovery, de novo design and optimization of several CK2 inhibitors, active in the low nanomolar range...
February 20, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28230321/disruption-of-genes-involved-in-corvet-complex-leads-to-enhanced-secretion-of-heterologous-carboxylesterase-only-in-protease-deficient-pichia-pastoris
#5
Lukas Marsalek, Clemens Gruber, Friedrich Altmann, Markus Aleschko, Diethard Mattanovich, Brigitte Gasser, Verena Puxbaum
The methylotrophic yeast Pichia pastoris (Komagataella spp.) is a popular microbial host for the production of recombinant proteins. Previous studies have shown that mis-sorting to the vacuole can be a bottleneck during production of recombinant secretory proteins in yeast, however, no information was available for P. pastoris. In this work we have therefore generated vps (vacuolar protein sorting) mutant strains disrupted in genes involved in the CORVET tethering complex at the early stages of endosomal sorting...
February 23, 2017: Biotechnology Journal
https://www.readbyqxmd.com/read/28230157/highly-sensitive-and-adaptable-fluorescence-quenched-pair-discloses-the-substrate-specificity-profiles-in-diverse-protease-families
#6
Marcin Poreba, Aleksandra Szalek, Wioletta Rut, Paulina Kasperkiewicz, Izabela Rutkowska-Wlodarczyk, Scott J Snipas, Yoshifumi Itoh, Dusan Turk, Boris Turk, Christopher M Overall, Leszek Kaczmarek, Guy S Salvesen, Marcin Drag
Internally quenched fluorescent (IQF) peptide substrates originating from FRET (Förster Resonance Energy Transfer) are powerful tool for examining the activity and specificity of proteases, and a variety of donor/acceptor pairs are extensively used to design individual substrates and combinatorial libraries. We developed a highly sensitive and adaptable donor/acceptor pair that can be used to investigate the substrate specificity of cysteine proteases, serine proteases and metalloproteinases. This novel pair comprises 7-amino-4-carbamoylmethylcoumarin (ACC) as the fluorophore and 2,4-dinitrophenyl-lysine (Lys(DNP)) as the quencher...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28229167/mutation-in-a-highly-conserved-glycine-residue-in-strand-5b-of-plasminogen-activator-inhibitor-1-causes-polymerisation
#7
Takayuki Iwaki, Kotomi Nagahashi, Katsuhiro Takano, Katsue Suzuki-Inoue, Naohiro Kanayama, Kazuo Umemura, Tetsumei Urano
Serpinopathy is characterised as abnormal accumulation of serine protease inhibitors (SERPINs) in cells and results in clinical symptoms owing to lack of SERPIN function or excessive accumulation of abnormal SERPIN. We recently identified a patient with functional deficiency of plasminogen activator inhibitor-1 (PAI-1), a member of the SERPIN superfamily. The patient exhibited life-threatening bleeding tendencies, which have also been observed in patients with a complete deficiency in PAI-1. Sequence analysis revealed a homozygous single-nucleotide substitution from guanine to cytosine at exon 9, which changed amino acid residue 397 from glycine to arginine (c...
February 23, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28228845/histone-and-dna-methylation-control-by-h3-serine-10-threonine-11-phosphorylation-in-the-mouse-zygote
#8
Jie Lan, Konstantin Lepikhov, Pascal Giehr, Joern Walter
BACKGROUND: In the mammalian zygote, epigenetic reprogramming is a tightly controlled process of coordinated alterations of histone and DNA modifications. The parental genomes of the zygote show distinct patterns of histone H3 variants and distinct patterns of DNA and histone modifications. The molecular mechanisms linking histone variant-specific modifications and DNA methylation reprogramming during the first cell cycle remain to be clarified. RESULTS: Here, we show that the degree and distribution of H3K9me2 and of DNA modifications (5mC/5hmC) are influenced by the phosphorylation status of H3S10 and H3T11...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28228550/interaction-of-phosphorylated-rab11-fip2-with-eps15-regulates-apical-junction-composition
#9
Lynne A Lapierre, Elizabeth H Manning, Kenya M Mitchell, Cathy M Caldwell, James R Goldenring
MARK2 regulates the establishment of polarity in MDCK cells in part through phosphorylation of serine 227 of Rab11-FIP2. We have now identified Eps15 as an interacting partner of phospho-S227-Rab11-FIP2 (pS227-FIP2). During recovery from low calcium, Eps15 localized to the lateral membrane, prior to pS227-FIP2 arrival. Later in recovery, Eps15 and pS227-FIP2 co-localized at the lateral membrane. In MDCK cells expressing the pseudophosphorylated FIP2 mutant, FIP2(S227E), during recovery from low calcium, Eps15 was trapped and never localized to the lateral membrane...
February 22, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28228357/activation-of-mtor-i%C3%AE%C2%BAb-%C3%AE-nf-%C3%AE%C2%BAb-pathway-contributes-to-lps-induced-hypotension-and-inflammation-in-rats
#10
Meryem Temiz-Resitoglu, Sefika Pinar Kucukkavruk, Demet Sinem Guden, Pelin Cecen, Ayse Nihal Sari, Bahar Tunctan, Aysegul Gorur, Lulufer Tamer-Gumus, Cuneyt Kemal Buharalioglu, Kafait U Malik, Seyhan Sahan-Firat
Mammalian target of rapamycin (mTOR), a serine/threonine kinase plays an important role in various pathophysiological processes including cancer, metabolic diseases, and inflammation. Although mTOR participates in Toll-like receptor 4 signalling in different cell types, the role of this enzyme in sepsis pathogenesis and its effects on hypotension and inflammation in endotoxemic rats remains unclear. In this study we investigated the effects of mTOR inhibition on lipopolysaccharide (LPS)-induced changes on expressions and/or activities of ribosomal protein S6 (rpS6), an mTOR substrate, nuclear factor-κB (NF-κB) p65, inhibitor κB (IκB)-α, inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 with production of nitric oxide, peroxynitrite, prostacyclin, and tumor necrosis factor (TNF)-α and activity of myeloperoxidase (MPO), which results in hypotension and inflammation...
February 19, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28224917/regulation-of-the-wheat-map-kinase-phosphatase-1-by-14-3-3-proteins
#11
Mouna Ghorbel, Valérie Cotelle, Chantal Ebel, Ikram Zaidi, Mélanie Ormancey, Jean-Philippe Galaud, Moez Hanin
Plant MAP kinase phosphatases (MKPs) are major regulators of MAPK signaling pathways and play crucial roles in controlling growth, development and stress responses. The presence of several functional domains in plant MKPs such as a dual specificity phosphatase catalytic domain, gelsolin, calmodulin-binding and serine-rich domains, suggests that MKPs can interact with distinct cellular partners, others than MAPKs. In this report, we identified a canonical mode I 14-3-3-binding motif (574KLPSLP579) located at the carboxy-terminal region of the wheat MKP, TMKP1...
April 2017: Plant Science: An International Journal of Experimental Plant Biology
https://www.readbyqxmd.com/read/28224476/protein-phosphatase-2a-a-double-faced-phosphatase-of-cellular-system-and-its-role-in-neurodegenerative-disorders
#12
REVIEW
Md Nematullah, M N Hoda, Farah Khan
Protein phosphatase 2A (PP2A), a ubiquitously expressed serine/threonine phosphatase, is a vitally important phosphatase for the cellular system. Structurally, it is constituted of three different subunits, namely catalytic subunit (PP2Ac), structural scaffold subunit (PP2A-A), and regulatory subunit (PP2A-B). All subunits have various isoforms, and catalytic and scaffold subunits are ubiquitously expressed, whereas regulatory subunits are more specific to tissue and cell type. It is the numerous possibilities of PP2A holoenzyme assembly with varying isoform components that make it possess a dual nature of activator or the inhibitory character in different signaling pathways, namely neural developmental pathways, Akt/protein kinase B pathway, NF-kB pathway, MAPK pathway, apoptosis pathway, and cell cycle progression to name a few...
February 21, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28224230/newly-isolated-bacillus-sp-g51-from-patagonian-wool-produces-an-enzyme-combination-suitable-for-felt-resist-treatments-of-organic-wool
#13
Martín S Iglesias, Cynthia Sequeiros, Sebastián García, Nelda L Olivera
Bacteria from Patagonian Merino wool were isolated to assess their wool-keratinolytic activity and potential for felt-resist treatments. Strains from Bacillus, Exiguobacterium, Deinococcus, and Micrococcus produced wool-degrading enzymes. Bacillus sp. G51 showed the highest wool-keratinolytic activity. LC-MS/MS analysis revealed that G51 secreted two serine proteases belonging to the peptidase family S8 (MEROPS) and a metalloprotease associated with Bacillolysin, along with other enzymes (γ-glutamyltranspeptidase and dihydrolipoyl dehydrogenases) that could be involved in reduction of keratin disulfide bonds...
February 21, 2017: Bioprocess and Biosystems Engineering
https://www.readbyqxmd.com/read/28224044/mastl-is-essential-for-anaphase-entry-of-proliferating-primordial-germ-cells-and-establishment-of-female-germ-cells-in-mice
#14
Sanjiv Risal, Jingjing Zhang, Deepak Adhikari, Xiaoman Liu, Jingchen Shao, Mengwen Hu, Kiran Busayavalasa, Zhaowei Tu, Zijiang Chen, Philipp Kaldis, Kui Liu
In mammals, primordial germ cells (PGCs) are the embryonic cell population that serve as germ cell precursors in both females and males. During mouse embryonic development, the majority of PGCs are arrested at the G2 phase when they migrate into the hindgut at 7.75-8.75 dpc (days post coitum). It is after 9.5 dpc that the PGCs undergo proliferation with a doubling time of 12.6 h. The molecular mechanisms underlying PGC proliferation are however not well studied. In this work. Here we studied how MASTL (microtubule-associated serine/threonine kinase-like)/Greatwall kinase regulates the rapid proliferation of PGCs...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28223969/mycobacterium-tuberculosis-prolyl-oligopeptidase-induces-in-vitro-secretion-of-proinflammatory-cytokines-by-peritoneal-macrophages
#15
Brina Portugal, Flávia N Motta, Andre F Correa, Diego O Nolasco, Hugo de Almeida, Kelly G Magalhães, Ana L V Atta, Francisco D Vieira, Izabela M D Bastos, Jaime M Santana
Tuberculosis (TB) is a disease that leads to death over 1 million people per year worldwide and the biological mediators of this pathology are poorly established, preventing the implementation of effective therapies to improve outcomes in TB. Host-bacterium interaction is a key step to TB establishment and the proteases produced by these microorganisms seem to facilitate bacteria invasion, migration and host immune response evasion. We presented, for the first time, the identification, biochemical characterization, molecular dynamics (MDs) and immunomodulatory properties of a prolyl oligopeptidase (POP) from Mycobacterium tuberculosis (POPMt)...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28223360/a-novel-subtilase-inhibitor-in-plants-shows-structural-and-functional-similarities-to-protease-propeptides
#16
Mathias Hohl, Annick Stintzi, Andreas Schaller
The propeptides of subtilisin-like serine proteinases (SBTs) serve dual functions as intramolecular chaperones that are required for enzyme folding and as inhibitors of the mature proteases. SBT propeptides are homologous to the I9 family of protease inhibitors that have only been described in fungi. Here we report the identification and characterization of Subtilisin Propeptide-Like Inhibitor 1 (SPI-1) from Arabidopsis thaliana. Sequence similarity and the shared β-α-β-β-α-β core structure identified SPI-1 as a member of the I9 inhibitor family, and as the first independent I9 inhibitor in higher eukaryotes...
February 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28223314/attenuation-of-epidermal-growth-factor-egf-signaling-by-growth-hormone-gh
#17
Lorena Gonzalez, Johanna Gabriela Miquet, Pablo E Irene, María Eugenia Díaz, Soledad P Rossi, Ana Isabel Sotelo, Mónica B Frungieri, Cristal M Hill, Andrzej Bartke, Daniel Turyn
Transgenic mice overexpressing growth hormone (GH) show increased hepatic protein content of the epidermal growth factor receptor (EGFR), which is broadly associated with cell proliferation and oncogenesis. However, chronically elevated levels of GH result in desensitization of STAT-mediated EGF signal and similar response of Erk1/2 and Akt signaling to EGF compared to normal mice. To ascertain the mechanisms involved in GH attenuation of EGF signaling and the consequences on cell cycle promotion, phosphorylation of signaling mediators was studied at different time points after EGF stimulation, and induction of proteins involved in cell cycle progression was assessed in normal and GH-overexpressing transgenic mice...
February 21, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28223215/bufadienolides-from-kalanchoe-daigremontiana-as-thrombin-inhibitors-in-vitro-and-in-silico-study
#18
Joanna Kolodziejczyk-Czepas, Malgorzata Sieradzka, Barbara Moniuszko-Szajwaj, Łukasz Pecio, Michal B Ponczek, Pawel Nowak, Anna Stochmal
Thrombin is an active plasma coagulation factor II, critical for the formation of fibrin clot during blood coagulation. For that reason, this protein is also a crucial target for different anti-thrombotic therapies. The work is based on in vitro evaluation of the inhibitory effect of bufadienolide-rich fraction, isolated from roots of Kalanchoe daigremontiana (1-50μg/ml) on enzymatic properties of a serine proteinase - thrombin. The efficacy of the inhibition of amidolytic activity of thrombin (measured as a hydrolysis of the chromogenic substrate S-2238, Chromogenix) attained about 10 and 66%, respectively...
February 18, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28222221/elastase-2-an-angiotensin-ii-generating-enzyme-contributes-to-increased-ang-ii-in-resistance-arteries-of-mice-with-myocardial-infarction
#19
Christiane Becari, Marcondes A B Silva, Marina T Durand, Cibele M Prado, Eduardo B Oliveira, Mauricio S Ribeiro, Helio C Salgado, Maria Cristina O Salgado, Rita C Tostes
Angiotensin II (Ang II), whose generation largely depends on angiotensin-converting enzyme activity, mediates most of the renin-angiotensin-system effects. Elastase-2 (ELA-2), a chymotrypsin-serine protease elastase family member 2A, alternatively generates Ang II in rat arteries. Myocardial infarction (MI) leads to intense RAS activation, but mechanisms involved on Ang II-generation in resistance arteries are unknown. We hypothesized that ELA-2 contributes to vascular Ang II generation and to cardiac damage in mice submitted to MI...
February 21, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28222195/autoantibodies-against-mono-and-tri-methylated-lysine-display-similar-but-also-distinctive-characteristics
#20
Zhiqiang Wang, Younan Ma, Fan Liu, Linjie Chen, Ruitong Gao, Wei Zhang
Autoantibodies can be either harmful or beneficial to the body. The beneficial autoantibodies play important roles in immunosurveillance, clearance of body waste and maintenance of immune homeostasis. Despite their importance, however, people's knowledge on the protective autoantibodies is still very limited. In the current study, we examined two autoantibodies that recognized epitopes with only one amino acid. One was against mono-methylated lysine (Kme) and the other was against tri-methylated lysine (Kme3)...
2017: PloS One
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