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https://www.readbyqxmd.com/read/28821859/reduction-of-the-off-pathway-iron-sulphur-cluster-n1a-of-escherichia-coli-respiratory-complex-i-restrains-nad-dissociation
#1
Emmanuel Gnandt, Johannes Schimpf, Caroline Harter, Jo Hoeser, Thorsten Friedrich
Respiratory complex I couples the electron transfer from NADH to ubiquinone with the translocation of protons across the membrane. The reaction starts with NADH oxidation by a flavin cofactor followed by transferring the electrons through a chain of seven iron-sulphur clusters to quinone. An eighth cluster called N1a is located proximally to flavin, but on the opposite side of the chain of clusters. N1a is strictly conserved although not involved in the direct electron transfer to quinone. Here, we show that the NADH:ferricyanide oxidoreductase activity of E...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821619/dsc-e3-ligase-localization-to-the-golgi-requires-the-atpase-cdc48-and-cofactor-ufd1-for-activation-of-sterol-regulatory-element-binding-protein-in-fission-yeast
#2
Risa Burr, Diedre Ribbens, Sumana Raychaudhuri, Emerson V Stewart, Jason Ho, Peter J Espenshade
Sterol regulatory element-binding proteins (SREBPs) in the fission yeast Schizosaccharomyces pombe regulate lipid homeostasis and the hypoxic response under conditions of low sterol or oxygen availability. SREBPs are cleaved in the Golgi through the combined action of the Dsc E3 ligase complex, the rhomboid protease Rbd2, and the essential ATPases Associated with diverse cellular Activities (AAA+) ATPase Cdc48. The soluble SREBP N-terminal transcription factor domain is then released in the cytosol to enter the nucleus and regulate gene expression...
August 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28821467/in-vitro-characterization-of-cyp102g4-from-streptomyces-cattleya-a-self-sufficient-p450-naturally-producing-indigo
#3
Joonwon Kim, Pyung-Gang Lee, Eun-Ok Jung, Byung-Gee Kim
Self-sufficient CYP102As possess outstanding hydroxylating activity to fatty acids such as myristic acid. Other CYP102 subfamily members share substrate specificity of CYP102As, but, occasionally, unusual characteristics of its own subfamily have been found. In this study, only one self-sufficient cytochrome P450 from Streptomyces cattleya was renamed from CYP102A_scat to CYP102G4, purified and characterized. UV-Vis spectrometry pattern, FAD/FMN analysis, and protein sequence comparison among CYP102s have shown that CYP102 from Streptomyces cattleya belongs to CYP102G subfamily...
August 15, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28821363/living-donor-kidney-transplantation-in-atypical-hemolytic-uremic-syndrome-a-case-series
#4
Caroline Duineveld, Jacobien C Verhave, Stefan P Berger, Nicole C A J van de Kar, Jack F M Wetzels
BACKGROUND: The development of complement inhibitors has greatly improved the outcome of patients with atypical hemolytic uremic syndrome (aHUS), making kidney transplantation a more feasible option. Although prophylactic eculizumab therapy may prevent recurrent disease after transplantation, its necessity for all transplant recipients is debated. STUDY DESIGN: A case series. SETTING & PARTICIPANTS: Patients with aHUS who underwent living donor kidney transplantation after 2011 at 2 university centers, prospectively followed up with a protocol of eculizumab therapy limited to only recipients with documented posttransplantation recurrent thrombotic microangiopathy...
August 16, 2017: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/28821129/characterization-and-anticoagulant-activity-of-a-fucosylated-chondroitin-sulfate-with-unusually-procoagulant-effect-from-sea-cucumber
#5
Mohamed Ben Mansour, Rafik Balti, Véronique Ollivier, Hichem Ben Jannet, Frédéric Chaubet, Raoui Mounir Maaroufi
The fucosylated chondroitin sulfate (FuCS) was isolated from the sea cucumber Holothuria polii body wall and then purified by anion exchange chromatography and the structure was characterized by FT-IR and NMR spectroscopy. Anticoagulant activity was measured in plasma by classical anticoagulation tests and the thrombin generation was assessed by calibrated automated thrombography. The results showed that the FuCS obtained at a yield of 4.66% possesses high sulfate content 43% and an average molecular mass of 45...
October 15, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28820334/evolutionary-analysis-of-a-novel-zinc-ribbon-in-the-n-terminal-region-of-threonine-synthase
#6
Gurmeet Kaur, Srikrishna Subramanian
Threonine synthase (TS) catalyzes the terminal reaction in the biosynthetic pathway of threonine and requires pyridoxal phosphate as a cofactor. TSs share a common catalytic domain with other fold type II PALP dependent enzymes. TSs are broadly grouped into two classes based on their sequence, quaternary structure, and enzyme regulation. We report the presence of a novel zinc ribbon domain in the N-terminal region preceding the catalytic core in TS. The zinc ribbon domain is present in TSs belonging to both classes...
August 18, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28819328/synthetic-models-for-nickel-iron-hydrogenase-featuring-redox-active-ligands
#7
David Schilter, Danielle L Gray, Amy L Fuller, Thomas B Rauchfuss
The nickel-iron hydrogenase enzymes efficiently and reversibly interconvert protons, electrons, and dihydrogen. These redox proteins feature iron-sulfur clusters that relay electrons to and from their active sites. Reported here are synthetic models for nickel-iron hydrogenase featuring redox-active auxiliaries that mimic the iron-sulfur cofactors. The complexes prepared are Ni(II)(μ-H)Fe(II)Fe(II) species of formula [(diphosphine)Ni(dithiolate)(μ-H)Fe(CO)2(ferrocenylphosphine)](+) or Ni(II)Fe(I)Fe(II) complexes [(diphosphine)Ni(dithiolate)Fe(CO)2(ferrocenylphosphine)](+) (diphosphine = Ph2P(CH2)2PPh2 or Cy2P(CH2)2PCy2; dithiolate = (-)S(CH2)3S(-); ferrocenylphosphine = diphenylphosphinoferrocene, diphenylphosphinomethyl(nonamethylferrocene) or 1,1'-bis(diphenylphosphino)ferrocene)...
May 2017: Australian Journal of Chemistry
https://www.readbyqxmd.com/read/28819009/the-aaa-atpase-p97-a-cellular-multitool
#8
REVIEW
Lasse Stach, Paul S Freemont
The AAA+ (ATPases associated with diverse cellular activities) ATPase p97 is essential to a wide range of cellular functions, including endoplasmic reticulum-associated degradation, membrane fusion, NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) activation and chromatin-associated processes, which are regulated by ubiquitination. p97 acts downstream from ubiquitin signaling events and utilizes the energy from ATP hydrolysis to extract its substrate proteins from cellular structures or multiprotein complexes...
August 17, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28818867/exploring-potential-germline-associated-roles-of-the-trim-nhl-protein-nhl-2%C3%A2-through-rnai-screening
#9
Gregory M Davis, Wai Y Low, Joshua W T Anderson, Peter R Boag
TRIM-NHL proteins are highly conserved regulators of developmental pathways in vertebrates and invertebrates. The TRIM-NHL family member, NHL-2 in Caenorhabditis elegans functions as a miRNA cofactor to regulate developmental timing. Similar regulatory roles have been reported in other model systems, with the mammalian orthologue in mice, TRIM32, contributing to muscle and neuronal cell proliferation via miRNA activity. Given the interest associated with TRIM-NHL family proteins, we aimed to further investigate the role of NHL-2 in C...
August 17, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28818555/pyridoxine-5-phosphate-oxidase-pnpo-deficiency-clinical-and-biochemical-alterations-associated-with-the-c-347g-a-p-%C3%A2-arg116gln-mutation
#10
Martino L di Salvo, Mario Mastrangelo, Isabel Nogués, Manuela Tolve, Alessandro Paiardini, Carla Carducci, Davide Mei, Martino Montomoli, Angela Tramonti, Renzo Guerrini, Roberto Contestabile, Vincenzo Leuzzi
BACKGROUND: Pyridoxal-5(')-phosphate oxidase (PNPO) deficiency presents as a severe neonatal encephalopathy responsive to pyridoxal-5(')-phosphate (PLP) or pyridoxine. Recent studies widened the phenotype of this condition and detected genetic variants on PNPO gene whose pathogenic role and clinical expression remain to be established. OBJECTIVE: This paper aims to characterize the functional effects of the c.347G>A (p.Arg116Gln) mutation in the PNPO gene in order to define its pathogenicity and describe the clinical features of new patients with epilepsy carrying this mutation...
August 12, 2017: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/28817720/targeting-of-cdk9-with-indirubin-3-monoxime-safely-and-durably-reduces-hiv-viremia-in-chronically-infected-humanized-mice
#11
Sandra Medina-Moreno, Thomas C Dowling, Juan C Zapata, Nhut M Le, Edward Sausville, Joseph Bryant, Robert R Redfield, Alonso Heredia
Successful propagation of HIV in the human host requires entry into a permissive cell, reverse transcription of viral RNA, integration into the human genome, transcription of the integrated provirus, and assembly/release of new virus particles. Currently, there are antiretrovirals against each of these viral steps, except for provirus transcription. An inhibitor of HIV transcription could both increase potency of treatment and suppress drug-resistant strains. Cellular cyclin-dependent kinase 9 (CDK9) serves as a cofactor for the HIV Tat protein and is required for effective transcription of the provirus...
2017: PloS One
https://www.readbyqxmd.com/read/28815021/toward-an-understanding-of-the-cdc48-p97-atpase
#12
REVIEW
Nicholas Bodnar, Tom Rapoport
A conserved AAA+ ATPase, called Cdc48 in yeast and p97 or VCP in metazoans, plays an essential role in many cellular processes by segregating polyubiquitinated proteins from complexes or membranes. For example, in endoplasmic reticulum (ER)-associated protein degradation (ERAD), Cdc48/p97 pulls polyubiquitinated, misfolded proteins out of the ER and transfers them to the proteasome. Cdc48/p97 consists of an N-terminal domain and two ATPase domains (D1 and D2). Six Cdc48 monomers form a double-ring structure surrounding a central pore...
2017: F1000Research
https://www.readbyqxmd.com/read/28814513/escape-of-tick-borne-flavivirus-from-2-c-methylated-nucleoside-antivirals-is-mediated-by-a-single-conservative-mutation-in-ns5-that-has-a-dramatic-effect-on-viral-fitness
#13
Ludek Eyer, Hirofumi Kondo, Darina Zouharova, Minato Hirano, James J Valdés, Memi Muto, Tomas Kastl, Shintaro Kobayashi, Jan Haviernik, Manabu Igarashi, Hiroaki Kariwa, Marketa Vaculovicova, Jiri Cerny, Rene Kizek, Andrea Kröger, Stefan Lienenklaus, Milan Dejmek, Radim Nencka, Martin Palus, Jiri Salat, Erik De Clercq, Kentaro Yoshii, Daniel Ruzek
Tick-borne encephalitis virus (TBEV) causes a severe and potentially fatal neuroinfection in humans. Despite its high medical relevance, no specific antiviral therapy is currently available. Here we demonstrate that treatment with a nucleoside analog, 7-deaza-2' -C-methyladenosine (7-deaza-2' -CMA), substantially improved disease outcome, increased survival, and reduced signs of neuroinfection and viral titers in the brains of mice infected with a lethal dose of TBEV. To investigate the mechanism of action of 7-deaza-2' -CMA, two drug-resistant TBEV clones were generated and characterized...
August 16, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28814508/dynamic-functional-assembly-of-the-torsin-aaa-atpase-and-its-modulation-by-lap1
#14
Anna R Chase, Ethan Laudermilch, Jimin Wang, Hideki Shigematsu, Takeshi Yokoyama, Christian Schlieker
TorsinA is an essential AAA+ ATPase requiring LAP1 or LULL1 as cofactors. The dynamics of the Torsin/cofactor system remain poorly understood, with previous models invoking Torsin/cofactor assemblies with fixed stoichiometries. Here, we demonstrate that TorsinA assembles into homotypic oligomers in the presence of ATP. Torsin variants mutated at the 'back' interface disrupt homo-oligomerization but still show robust ATPase activity in the presence of its cofactors. These Torsin mutants are severely compromised in their ability to rescue nuclear envelope defects in Torsin-deficient cells, suggesting that TorsinA homo-oligomers play a key role in vivo Engagement of the oligomer by LAP1 triggers ATP hydrolysis and rapid complex disassembly...
August 16, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28813411/mammals-divert-endogenous-genotoxic-formaldehyde-into-one-carbon-metabolism
#15
Guillermo Burgos-Barragan, Niek Wit, Johannes Meiser, Felix A Dingler, Matthias Pietzke, Lee Mulderrig, Lucas B Pontel, Ivan V Rosado, Thomas F Brewer, Rebecca L Cordell, Paul S Monks, Christopher J Chang, Alexei Vazquez, Ketan J Patel
The folate-driven one-carbon (1C) cycle is a fundamental metabolic hub in cells that enables the synthesis of nucleotides and amino acids and epigenetic modifications. This cycle might also release formaldehyde, a potent protein and DNA crosslinking agent that organisms produce in substantial quantities. Here we show that supplementation with tetrahydrofolate, the essential cofactor of this cycle, and other oxidation-prone folate derivatives kills human, mouse and chicken cells that cannot detoxify formaldehyde or that lack DNA crosslink repair...
August 16, 2017: Nature
https://www.readbyqxmd.com/read/28812125/recombinant-expression-and-biochemical-characterization-of-mycobacterium-tuberculosis-3fe-4s-ferredoxin-rv1786
#16
Yun Lu, Feng Qiao, Yue Li, Xiao-Hong Sang, Cong-Ran Li, Jian-Dong Jiang, Xin-Yi Yang, Xue-Fu You
Ferredoxins are iron-sulfur protein that mediate electron transfer in cytochrome P450 mono-oxygenase (CYP)-related catalytic reactions in a wide variety of organisms. Rv1786 is a putative ferredoxin, encoded by a gene located downstream of the gene encoding CYP143A1 in the Mycobacterium tuberculosis genome. However, the structure and function of Rv1786 have remained unclear. Here, the recombinant Mtb Rv1786 was expressed, purified as a His-tagged form and characterized with [3Fe-4S] clusters as its cofactors using a series of measurements including SDS-PAGE, western blot, UV/Visible, MALDI-TOF/TOF-MS, and electron paramagnetic resonance spectroscopic analysis...
August 15, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28811613/transcriptomic-analysis-of-nickel-exposure-in-sphingobium-sp-ba1-cells-using-rna-seq
#17
M Volpicella, C Leoni, C Manzari, M Chiara, E Picardi, E Piancone, F Italiano, A D'Erchia, M Trotta, D S Horner, G Pesole, L R Ceci
Nickel acts as cofactor for a number of enzymes of many bacteria species. Its homeostasis is ensured by proteins working as ion efflux or accumulation systems. These mechanisms are also generally adopted to counteract life-threatening high extra-cellular Ni(2+) concentrations. Little is known regarding nickel tolerance in the genus Sphingobium. We studied the response of the novel Sphingobium sp. ba1 strain, able to adapt to high Ni(2+) concentrations. Differential gene expression in cells cultured in 10 mM Ni(2+), investigated by RNA-seq analysis, identified 118 differentially expressed genes...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28809129/effect-of-methotrexate-vitamin-b12-on-dna-methylation-as-a-potential-factor-in-leukemia-treatment-related-neurotoxicity
#18
Victoria J Forster, Alex McDonnell, Rachel Theobald, Jill A McKay
Methotrexate (MTX) is administered to treat childhood acute lymphoblastic leukemia (ALL). It acts by inhibiting dihydrofolate reductase which reduces methyltetrahydrofolate, a key component in one carbon metabolism, thus reducing cell proliferation. Further perturbations to one carbon metabolism, such as reduced vitamin B12 levels via the use of nitrous oxide for sedation during childhood ALL treatment, may increase neurotoxicity risk. With B12 as an enzymatic cofactor, methyltetrahydrofolate is essential to produce methionine, which is critical for DNA methylation...
August 15, 2017: Epigenomics
https://www.readbyqxmd.com/read/28808922/backbone-resonance-assignments-for-the-set-domain-of-human-methyltransferase-nsd3-in-complex-with-its-cofactor
#19
Yan Li, Hui Qi Ng, Anna Ngo, Shuang Liu, Yih Wan Tan, Perlyn Zekui Kwek, Alvin W Hung, Joma Joy, Jeffrey Hill, Thomas H Keller, CongBao Kang
NSD3 is a histone H3 methyltransferase that plays an important role in chromatin biology. A construct containing the methyltransferase domain encompassing residues Q1049-K1299 of human NSD3 was obtained and biochemical activity was demonstrated using histone as a substrate. Here we report the backbone HN, N, Cα, C', and side chain Cβ assignments of the construct in complex with S-adenosyl-L-methionine (SAM). Based on these assignments, secondary structures of NSD3/SAM complex in solution were determined.
August 14, 2017: Biomolecular NMR Assignments
https://www.readbyqxmd.com/read/28808239/compound-a-influences-gene-regulation-of-the-dexamethasone-activated-glucocorticoid-receptor-by-alternative-cofactor-recruitment
#20
S J Desmet, N Bougarne, L Van Moortel, L De Cauwer, J Thommis, M Vuylsteke, D Ratman, R Houtman, J Tavernier, K De Bosscher
The glucocorticoid receptor (GR) is a transcription factor of which the underlying gene regulatory mechanisms are complex and incompletely understood. The non-steroidal anti-inflammatory Compound A (CpdA), a selective GR modulating compound in various cell models, has been shown to favour GR-mediated gene repression but not GR-mediated gene activation. Shifting balances towards only a particular subset of GR gene regulatory events may be of benefit in the treatment of inflammatory diseases. We present evidence to support that the combination of CpdA with Dexamethasone (DEX), a classic steroidal GR ligand, can shape GR function towards a unique gene regulatory profile in a cell type-dependent manner...
August 14, 2017: Scientific Reports
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