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https://www.readbyqxmd.com/read/27932461/structural-characterization-and-ligand-inhibitor-identification-provide-functional-insights-into-the-mycobacterium-tuberculosis-cytochrome-p450-cyp126a1
#1
Jude T Chenge, Duyet Van Le, Shalini Swami, Kirsty J McLean, Madeline E Kavanagh, Anthony G Coyne, Stephen E J Rigby, Myles R Cheesman, Hazel M Girvan, Colin W Levy, Bernd Rupp, Jens P von Kries, Chris Abell, David Leys, Andrew W Munro
The Mycobacterium tuberculosis (Mtb) H37Rv genome encodes 20 cytochromes P450, including P450s crucial to infection and bacterial viability. Many Mtb P450s remain uncharacterized, suggesting their further analysis may provide new insights into Mtb metabolic processes and new targets for drug discovery. CYP126A1 is representative of a P450 family widely distributed in mycobacteria and other bacteria. Here we explore the biochemical and structural properties of CYP126A1, including its interactions with new chemical ligands...
December 8, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27912006/cascading-effects-of-predation-risk-determine-how-marine-predators-become-terrestrial-prey-on-an-oceanic-island
#2
Sarah K Thomsen, David J Green
Apex predators can suppress the foraging activity of mesopredators, which may then result in cascading benefits for the prey of those mesopredators. We studied the interactions between a top predator, the Barn Owl (Tyto alba), and their primary prey, an island endemic deer mouse (Peromyscus maniculatus elusus), which in turn consumes the eggs of seabirds nesting on Santa Barbara Island in California. Scripps's Murrelets (Synthliboramphus scrippsi), a threatened nocturnal seabird, arrive annually to breed on this island, and whose first egg is particularly vulnerable to predation by mice...
December 2016: Ecology
https://www.readbyqxmd.com/read/27899560/not5-dependent-co-translational-assembly-of-ada2-and-spt20-is-essential-for-functional-integrity-of-saga
#3
Sari Kassem, Zoltan Villanyi, Martine A Collart
Acetylation of histones regulates gene expression in eukaryotes. In the yeast Saccharomyces cerevisiae it depends mainly upon the ADA and SAGA histone acetyltransferase complexes for which Gcn5 is the catalytic subunit. Previous screens have determined that global acetylation is reduced in cells lacking subunits of the Ccr4-Not complex, a global regulator of eukaryotic gene expression. In this study we have characterized the functional connection between the Ccr4-Not complex and SAGA. We show that SAGA mRNAs encoding a core set of SAGA subunits are tethered together for co-translational assembly of the encoded proteins...
November 28, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27885629/glutaminases
#4
Javier Márquez, José M Matés, José A Campos-Sandoval
Mammalian glutaminases catalyze the stoichiometric conversion of L-glutamine to L-glutamate and ammonium ions. In brain, glutaminase is considered the prevailing pathway for synthesis of the neurotransmitter pool of glutamate. Besides neurotransmission, the products of glutaminase reaction also fulfill crucial roles in energy and metabolic homeostasis in mammalian brain. In the last years, new functional roles for brain glutaminases are being uncovered by using functional genomic and proteomic approaches. Glutaminases may act as multifunctional proteins able to perform different tasks: the discovery of multiple transcript variants in neurons and glial cells, novel extramitochondrial localizations, and isoform-specific proteininteracting partners strongly support possible moonlighting functions for these proteins...
2016: Advances in Neurobiology
https://www.readbyqxmd.com/read/27882614/%C3%AE-ketoglutarate-dehydrogenase-complex-moonlighting-ros-signalling-added-to-the-list-an-editorial-highlight-for-reductions-in-the-mitochondrial-enzyme-%C3%AE-ketoglutarate-dehydrogenase-complex-in-neurodegenerative-disease-beneficial-or-detrimental
#5
EDITORIAL
Emilio Fernandez, Juan P Bolaños
Read the highlighted article 'Reductions in the mitochondrial enzyme α-ketoglutarate dehydrogenase complex in neurodegenerative disease - beneficial or detrimental?' on page 823.
December 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27867805/isolation-of-lactic-acid-bacteria-bound-to-the-porcine-intestinal-mucosa-and-an-analysis-of-their-moonlighting-adhesins
#6
Hideki Kinoshita, Satoko Ohuchi, Kensuke Arakawa, Masamichi Watanabe, Haruki Kitazawa, Tadao Saito
The adhesion of lactic acid bacteria (LAB) to the intestinal mucosa is one of the criteria in selecting for probiotics. Eighteen LAB were isolated from porcine intestinal mucin (PIM): ten strains of Lactobacillus, six strains of Weissella, and two strains of Streptococcus. Using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) for phosphate-buffered saline (PBS) extracts from the LAB, many bands were detected in half of the samples, while a few and/or no clear bands were detected in the other half...
2016: Bioscience of Microbiota, Food and Health
https://www.readbyqxmd.com/read/27867042/poly-adp-ribose-polymerase-1-hyperactivation-in-neurodegenerative-diseases-the-death-knell-tolls-for-neurons
#7
REVIEW
Parimala Narne, Vimal Pandey, Praveen Kumar Simhadri, Prakash Babu Phanithi
Neurodegeneration is a salient feature of chronic refractory brain disorders like Alzheimer's, Parkinson's, Huntington's, amyotropic lateral sclerosis and acute conditions like cerebral ischemia/reperfusion etc. The pathological protein aggregates, mitochondrial mutations or ischemic insults typifying these disease conditions collude with and intensify existing oxidative stress and attendant mitochondrial dysfunction. Interlocking these mechanisms is poly(ADP-ribose) polymerase (PARP-1) hyperactivation that invokes a distinct form of neuronal cell death viz...
November 17, 2016: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/27865402/some-proteins-of-m-%C3%A2-tuberculosis-that-localise-to-the-nucleus-of-thp-1-derived-macrophages
#8
Atul Kumar Agrawal, Rajeev Ranjan, Sharat Chandra, Tofan Kumar Rout, Amit Misra, Thota Jagadeshwar Reddy
Host-pathogen dialectics in tuberculosis (TB) via DNA-protein interactions are emerging. We investigated whether proteins produced by Mycobacterium tuberculosis (Mtb) could translocate to the host nucleus. Using lysates of nuclei purified from Mtb-infected THP-1-derived macrophages, we identified at least 15 proteins of Mtb-origin by electrophoretic and chromatographic separation and mass spectrometry. Western blotting confirmed time-dependent accumulation of Mtb EF-Tu, GroEL, GroES and MtrA in the host nucleus...
December 2016: Tuberculosis
https://www.readbyqxmd.com/read/27853572/anthropogenic-disruption-of-the-night-sky-darkness-in-urban-and-rural-areas
#9
Salvador Bará
The growing emissions of artificial light to the atmosphere are producing, among other effects, a significant increase of the night sky brightness (NSB) above its expected natural values. A permanent sensor network has been deployed in Galicia (northwest of Iberian peninsula) to monitor the anthropogenic disruption of the night sky darkness in a countrywide area. The network is composed of 14 detectors integrated in automated weather stations of MeteoGalicia, the Galician public meteorological agency. Zenithal NSB readings are taken every minute and the results are openly available in real time for researchers, interested stakeholders and the public at large through a dedicated website...
October 2016: Royal Society Open Science
https://www.readbyqxmd.com/read/27833947/erythropoietin-and-co-intrinsic-structure-and-functional-disorder
#10
REVIEW
Vladimir N Uversky, Elrashdy M Redwan
Erythropoietin (Epo) is a heavily glycosylated protein, with its main function being related to erythropoiesis, where it controls red blood cell production via interaction with the Epo receptor (EpoR). It also plays a number of important roles in various hormonal, growth factor, and cytokine pathways. These roles are defined by Epo partners, such as the homodimeric (EpoR)2 receptor, the heterodimeric EpoR/βCR receptor and hypoxia inducing factor (HIF). Although the main structural features of both Epo and EpoR are conserved in vertebrates, the secretion sites of Epo in mammals are different from those in other vertebrates...
November 11, 2016: Molecular BioSystems
https://www.readbyqxmd.com/read/27808157/n-acetyl-ornithine-deacetylase-is-a-moonlighting-protein-and-is-involved-in-the-adaptation-of-entamoeba-histolytica-to-nitrosative-stress
#11
Preeti Shahi, Meirav Trebicz-Geffen, Shruti Nagaraja, Rivka Hertz, Sharon Alterzon-Baumel, Karen Methling, Michael Lalk, Mohit Mazumder, Gourinath Samudrala, Serge Ankri
Adaptation of the Entamoeba histolytica parasite to toxic levels of nitric oxide (NO) that are produced by phagocytes may be essential for the establishment of chronic amebiasis and the parasite's survival in its host. In order to obtain insight into the mechanism of E. histolytica's adaptation to NO, E. histolytica trophozoites were progressively adapted to increasing concentrations of the NO donor drug, S-nitrosoglutathione (GSNO) up to a concentration of 110 μM. The transcriptome of NO adapted trophozoites (NAT) was investigated by RNA sequencing (RNA-seq)...
November 3, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27742866/engineering-a-trifunctional-proline-utilization-a-chimera-by-fusing-a-dna-binding-domain-to-a-bifunctional-puta
#12
Benjamin W Arentson, Erin L Hayes, Weidong Zhu, Harkewal Singh, John J Tanner, Donald F Becker
Proline utilization A (PutA) is a bifunctional flavoenzyme with proline dehydrogenase (PRODH) and Δ(1)-pyrroline-5-carboxylate dehydrogenase domains that catalyzes the two-step oxidation of proline to glutamate. Trifunctional PutAs also have an N-terminal ribbon-helix-helix (RHH) DNA-binding domain and moonlight as autogenous transcriptional repressors of the put regulon. A unique property of trifunctional PutA is the ability to switch functions from DNA-bound repressor to membrane-associated enzyme in response to cellular nutritional needs and proline availability...
October 14, 2016: Bioscience Reports
https://www.readbyqxmd.com/read/27671864/challenging-drug-target-for-parkinson-s-disease-pathological-complex-of-the-chameleon-tppp-p25-and-alpha-synuclein-proteins
#13
Tibor Szénási, Judit Oláh, Adél Szabó, Sándor Szunyogh, András Láng, András Perczel, Attila Lehotzky, Vladimir N Uversky, Judit Ovádi
The hallmarks of Parkinson's disease and other synucleinopathies, Tubulin Polymerization Promoting Protein (TPPP/p25) and α-synuclein (SYN) have two key features: they are disordered and co-enriched/co-localized in brain inclusions. These Neomorphic Moonlighting Proteins display both physiological and pathological functions due to their interactions with distinct partners. To achieve the selective targeting of the pathological TPPP/p25-SYN but not the physiological TPPP/p25-tubulin complex, their interfaces were identified as a specific innovative strategy for the development of anti-Parkinson drugs...
September 24, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27651759/volume-transmission-and-receptor-receptor-interactions-in-heteroreceptor-complexes-understanding-the-role-of-new-concepts-for-brain-communication
#14
REVIEW
Kjell Fuxe, Dasiel O Borroto-Escuela
The discovery of the central monoamine neurons not only demonstrated novel types of brain stem neurons forming global terminal networks all over the brain and the spinal cord, but also to a novel type of communication called volume transmission. It is a major mode of communication in the central nervous system that takes places in the extracellular fluid and the cerebral spinal fluid through diffusion and flow of molecules, like neurotransmitters and extracellular vesicles. The integration of synaptic and volume transmission takes place through allosteric receptor-receptor interactions in heteroreceptor complexes...
August 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/27638863/facin-a-double-edged-sword-of-the-emerging-periodontal-pathogen-filifactor-alocis-a-metabolic-enzyme-moonlighting-as-a-complement-inhibitor
#15
Monika Jusko, Beata Miedziak, David Ermert, Michal Magda, Ben C King, Ewa Bielecka, Kristian Riesbeck, Sigrun Eick, Jan Potempa, Anna M Blom
Periodontal disease is one of the most common inflammatory infectious diseases worldwide and it is associated with other syndromes, such as cardiovascular disease or rheumatoid arthritis. Recent advances in sequencing allowed for identification of novel periodontopathogens such as Gram-positive Filifactor alocis, but its virulence mechanisms remain largely unknown. We confirmed that F. alocis is a prevalent species in periodontitis patients, and we also observed strong correlation of this bacterium with clinical parameters, highlighting its role in the pathogenesis of the disease...
October 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27617777/the-die-is-cast-precision-electrophilic-modifications-contribute-to-cellular-decision-making
#16
Marcus J C Long, Yimon Aye
This perspective sets out to critically evaluate the scope of reactive electrophilic small molecules as unique chemical signal carriers in biological information transfer cascades. We consider these electrophilic cues as a new volatile cellular currency and compare them to canonical signaling circulation such as phosphate in terms of chemical properties, biological specificity, sufficiency, and necessity. The fact that nonenzymatic redox sensing properties are found in proteins undertaking varied cellular tasks suggests that electrophile signaling is a moonlighting phenomenon manifested within a privileged set of sensor proteins...
October 2, 2016: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/27617755/sequence-variation-between-462-human-individuals-fine-tunes-functional-sites-of-rna-processing
#17
Pedro G Ferreira, Martin Oti, Matthias Barann, Thomas Wieland, Suzana Ezquina, Marc R Friedländer, Manuel A Rivas, Anna Esteve-Codina, Philip Rosenstiel, Tim M Strom, Tuuli Lappalainen, Roderic Guigó, Michael Sammeth
Recent advances in the cost-efficiency of sequencing technologies enabled the combined DNA- and RNA-sequencing of human individuals at the population-scale, making genome-wide investigations of the inter-individual genetic impact on gene expression viable. Employing mRNA-sequencing data from the Geuvadis Project and genome sequencing data from the 1000 Genomes Project we show that the computational analysis of DNA sequences around splice sites and poly-A signals is able to explain several observations in the phenotype data...
September 12, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27606486/an-alternative-mode-of-cd43-signal-transduction-activates-pro-survival-pathways-of-t-lymphocytes
#18
Maria Elena Bravo-Adame, Rosario Vera-Estrella, Bronwyn J Barkla, Cecilia Martínez-Campos, Angel Flores-Alcantar, Jose Pablo Ocelotl-Oviedo, Gustavo Pedraza-Alva, Yvonne Rosenstein
CD43 is one of the most abundant co-stimulatory molecules on a T-cell surface; it transduces activation signals through its cytoplasmic domain, contributing to modulation of the outcome of T-cell responses. The aim of this study was to uncover new signalling pathways regulated by this sialomucin. Analysis of changes in protein abundance allowed us to identify pyruvate kinase isozyme M2 (PKM2), an enzyme of the glycolytic pathway, as an element potentially participating in the signalling cascade resulting from the engagement of CD43 and the T-cell receptor (TCR)...
January 2017: Immunology
https://www.readbyqxmd.com/read/27603308/rhamnose-links-moonlighting-proteins-to-membrane-phospholipid-in-mycoplasmas
#19
James M Daubenspeck, Runhua Liu, Kevin Dybvig
Many proteins that have a primary function as a cytoplasmic protein are known to have the ability to moonlight on the surface of nearly all organisms. An example is the glycolytic enzyme enolase, which can be found on the surface of many types of cells from bacteria to human. Surface enolase is not enzymatic because it is monomeric and oligomerization is required for glycolytic activity. It can bind various molecules and activate plasminogen. Enolase lacks a signal peptide and the mechanism by which it attaches to the surface is unknown...
2016: PloS One
https://www.readbyqxmd.com/read/27590660/identification-of-pathogenic-factors-potentially-involved-in-staphylococcus-aureus-keratitis-using-proteomics
#20
Shamila Khan, Nerida Cole, Emma B H Hume, Linda L Garthwaite, Terry Nguyen-Khuong, Bradley J Walsh, Mark D P Willcox
Staphylococcus is a leading cause of microbial keratitis, characterized by destruction of the cornea by bacterial exoproteins and host-associated factors. The aim of this study was to compare extracellular and cell-associated proteins produced by two different isolates of S. aureus, a virulent clinical isolate (Staph 38) and a laboratory strain (Staphylococcus aureus 8325-4) of weaker virulence in the mouse keratitis model. Proteins were analyzed using 2D polyacrylamide gel electrophoresis and identified by subsequent mass spectrometry...
October 2016: Experimental Eye Research
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