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https://www.readbyqxmd.com/read/28544736/molybdenum-cofactor-deficiency-identification-of-a-patient-with-homozygote-mutation-in-the-mocs3-gene
#1
Jan G M Huijmans, Rachel Schot, Johannis B C de Klerk, Monique Williams, René F M de Coo, Marinus Duran, Frans W Verheijen, Marjon van Slegtenhorst, Grazia M S Mancini
We describe the clinical presentation and 17 years follow up of a boy, born to consanguineous parents and presenting with intellectual disability (ID), autism, "marfanoid" dysmorphic features, and moderate abnormalities of sulfite metabolism compatible with molybdenum cofactor deficiency, but normal sulfite oxidase activity in cultured skin fibroblasts. Genomic exome analysis revealed a homozygous MOCS3 missense mutation, leading to a p.Ala257Thr substitution in the highly conserved ubiquitin-like-domain of the protein...
June 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28544649/activation-of-co2-by-vanadium-nitrogenase
#2
Nathaniel Sickerman, Yilin Hu, Markus Walter Ribbe
The reduction of CO2 into useful products, including hydrocarbon fuels, is an ongoing area of particular interest due to efforts to mitigate buildup of this greenhouse gas. While the industrial Fischer-Tropsch process can facilitate the hydrogenation of CO2 with H2 to form short-chain hydrocarbon products under high temperatures and pressures, a desire to perform these reactions under ambient conditions has inspired the use of biological approaches. Particularly, enzymes offer insight into how to activate and reduce CO2, but only one enzyme, nitrogenase, can perform the multielectron, multiproton reduction of CO¬2 into hydrocarbons...
May 22, 2017: Chemistry, An Asian Journal
https://www.readbyqxmd.com/read/28544589/methionine-tumor-starvation-by-erythrocyte-encapsulated-methionine-gamma-lyase-activity-controlled-with-per-os-vitamin-b6
#3
Fabien Gay, Karine Aguera, Karine Sénéchal, Angie Tainturier, Willy Berlier, Delphine Maucort-Boulch, Jérôme Honnorat, Françoise Horand, Yann Godfrin, Vanessa Bourgeaux
Erymet is a new therapy resulting from the encapsulation of a methionine gamma-lyase (MGL; EC number 4.4.1.11) in red blood cells (RBC). The aim of this study was to evaluate erymet potential efficacy in methionine (Met)-dependent cancers. We produced a highly purified MGL using a cGMP process, determined the pharmacokinetics/pharmacodynamics (PK/PD) properties of erymet in mice, and assessed its efficacy on tumor growth prevention. Cytotoxicity of purified MGL was tested in six cancer cell lines. CD1 mice were injected with single erymet product supplemented or not with vitamin B6 vitamer pyridoxine (PN; a precursor of PLP cofactor)...
May 23, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28544236/clinical-and-laboratory-phenotype-variability-in-type-2m-von-willebrand-disease
#4
Ashley L Doruelo, Sandra L Haberichter, Pamela A Christopherson, Lisa N Boggio, Sweta Gupta, Steven R Lentz, Amy D Shapiro, Robert R Montgomery, Veronica H Flood
BACKGROUND: Von Willebrand factor (VWF) is a multimeric coagulation factor that tethers platelets to injured subendothelium. Type 2M von Willebrand Disease (VWD) is characterized by a qualitative defect in VWF with preserved multimer distribution. OBJECTIVES: Through the Zimmerman Program for the Molecular and Clinical Biology for VWD, five VWF sequence variations were studied in subjects diagnosed with type 2M VWD. METHODS: Bleeding phenotype was assessed using the ISTH bleeding assessment tool...
May 20, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28544039/cofactor-free-direct-photoactivation-of-enoate-reductases-for-asymmetric-reduction-of-c-c-bonds
#5
Sahng Ha Lee, Da Som Choi, Milja Pesic, Yang Woo, Caroline Paul, Frank Hollmann, Chan Beum Park
Enoate reductases from the family of Old Yellow Enzymes (OYEs) can catalyze stereoselective trans-hydrogenation of activated C=C bonds. Here, we report visible light-driven activation of OYEs through NAD(P)H-free, direct transfer of photoexcited electrons from xanthene dyes to the prosthetic flavin moiety. Our spectroscopic and electrochemical analyses verified spontaneous association of rose bengal and its derivatives with OYEs. Illumination of a white light-emitting-diode triggered photoreduction of OYEs by xanthene dyes, which facilitated the enantioselective reduction of C=C bonds in the absence of NADH...
May 23, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28542723/spectroscopic-evidence-for-the-presence-of-a-high-valent-fe-iv-species-in-the-ferroxidase-reaction-of-an-archaeal-ferritin
#6
Kourosh Honarmand Ebrahimi, Eckhard Bill, Peter-Leon Hagedoorn, Wilfred R Hagen
A high-valent Fe(IV) species is proposed to be generated from the decay of a peroxodiferric intermediate in the catalytic cycle at the di-iron cofactor center of dioxygen activating enzymes such as methane monooxygenase. However, it is believed that this intermediate is not formed in the di-iron substrate site of ferritin, where oxidation of Fe(II) substrate to Fe(III) (ferroxidase reaction) occurs also via a peroxodiferric intermediate. In opposition to this generally accepted view, here we present evidence for the occurrence of a high-valent Fe(IV) in the ferroxidase reaction of an archaeal ferritin, which is based on trapped intermediates obtained with the freeze-quench technique and combination of spectroscopic characterization...
May 25, 2017: FEBS Letters
https://www.readbyqxmd.com/read/28542603/a-conformational-switch-high-throughput-screening-assay-and-allosteric-inhibition-of-the-flavivirus-ns2b-ns3-protease
#7
Matthew Brecher, Zhong Li, Binbin Liu, Jing Zhang, Cheri A Koetzner, Adham Alifarag, Susan A Jones, Qishan Lin, Laura D Kramer, Hongmin Li
The flavivirus genome encodes a single polyprotein precursor requiring multiple cleavages by host and viral proteases in order to produce the individual proteins that constitute an infectious virion. Previous studies have revealed that the NS2B cofactor of the viral NS2B-NS3 heterocomplex protease displays a conformational dynamic between active and inactive states. Here, we developed a conformational switch assay based on split luciferase complementation (SLC) to monitor the conformational change of NS2B and to characterize candidate allosteric inhibitors...
May 25, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28542187/elucidation-of-new-condition-dependent-roles-for-fructose-1-6-bisphosphatase-linked-to-cofactor-balances
#8
Du Toit W P Schabort, Stephanus G Kilian, James C du Preez
The cofactor balances in metabolism is of paramount importance in the design of a metabolic engineering strategy and understanding the regulation of metabolism in general. ATP, NAD+ and NADP+ balances are central players linking the various fluxes in central metabolism as well as biomass formation. NADP+ is especially important in the metabolic engineering of yeasts for xylose fermentation, since NADPH is required by most yeasts in the initial step of xylose utilisation, including the fast-growing Kluyveromyces marxianus...
2017: PloS One
https://www.readbyqxmd.com/read/28541545/kr%C3%A3-ppel-like-factors-compete-for-promoters-and-enhancers-to-fine-tune-transcription
#9
Melissa D Ilsley, Kevin R Gillinder, Graham W Magor, Stephen Huang, Timothy L Bailey, Merlin Crossley, Andrew C Perkins
Krüppel-like factors (KLFs) are a family of 17 transcription factors characterized by a conserved DNA-binding domain of three zinc fingers and a variable N-terminal domain responsible for recruiting cofactors. KLFs have diverse functions in stem cell biology, embryo patterning, and tissue homoeostasis. KLF1 and related family members function as transcriptional activators via recruitment of co-activators such as EP300, whereas KLF3 and related members act as transcriptional repressors via recruitment of C-terminal Binding Proteins...
May 24, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28540433/altered-tetrahydrobiopterin-metabolism-in-patients-with-phenylalanine-hydroxylase-deficiency
#10
Francesca Nardecchia, Flavia Chiarotti, Claudia Carducci, Silvia Santagata, Giulia Valentini, Antonio Angeloni, Nenad Blau, Vincenzo Leuzzi
The tetrahydrobiopterin (BH4) cofactor is essential for the activity of various enzymes, including phenylalanine (Phe) hydroxylase. In phenylketonuria (PKU) patients, who are chronically exposed to high Phe levels, high urinary excretion of BH4 metabolites neopterin and biopterin is observed. The aim of this longitudinal study was to investigate consistence and variability of the urinary excretion of pterins (neopterin and biopterin) in PKU patients in relation to age and concomitant blood Phe and tyrosine levels...
May 24, 2017: European Journal of Pediatrics
https://www.readbyqxmd.com/read/28540421/yeast-env9-encodes-a-conserved-lipid-droplet-ld-short-chain-dehydrogenase-involved-in-ld-morphology
#11
Ikha M Siddiqah, Surya P Manandhar, Stephanie M Cocca, Teli Hsueh, Vanessa Cervantes, Editte Gharakhanian
Lipid droplets (LDs) have emerged as dynamic and interactive organelles with important roles in lipid metabolism and membrane biogenesis. Here, we report that Saccharomyces cerevisiae Env9 is a novel conserved oxidoreductase involved in LD morphology. Microscopic and biochemical studies confirm localization of tagged Env9 to LDs and implicate its C-terminal hydrophobic domain (aa241-265) in its membrane association and stability. Confocal studies reveal a role for Env9 in LD morphology. Env9 positively affects both formation of large LDs upon overexpression and LD proliferation under poor carbon source...
May 24, 2017: Current Genetics
https://www.readbyqxmd.com/read/28539406/nek7-is-required-for-g1-progression-and-procentriole-formation
#12
Akshari Gupta, Yuki Tsuchiya, Midori Ohta, Gen Shiratsuchi, Daiju Kitagawa
The decision to commit to the cell cycle is made during G1 through the concerted action of various cyclin-CDK complexes. Not only DNA replication, but also centriole duplication is initiated as cells enter the S phase. The NIMA-related kinase NEK7 is one of the many factors that are required for proper centriole duplication, as well as timely cell cycle progression. However, its specific roles in these events remain poorly understood. In this study, we observed that the depletion of NEK7 inhibited progression through the G1 phase in human U2OS cells by the downregulation of various cyclins and CDKs, and also inhibited the earliest stages of procentriole formation...
May 24, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28539366/proteolytic-cleavage-orchestrates-cofactor-insertion-and-protein-assembly-in-nife-hydrogenase-biosynthesis
#13
Moritz Senger, Sven T Stripp, Basem Soboh
Metalloenzymes catalyze complex and essential processes such as photosynthesis, respiration, and nitrogen fixation. For example, bacteria and archaea use [NiFe]-hydrogenases to catalyze the uptake and release of molecular hydrogen (H2). [NiFe]-hydrogenases are redox enzymes composed of a large subunit that harbors a NiFe(CN)2CO metallo-center and a small subunit with three iron-sulfur clusters. The large subunit is synthesized with a C-terminal extension, cleaved off by a specific endopeptidase during maturation...
May 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28539363/identification-of-karyopherins-involved-in-the-nuclear-import-of-rna-exosome-subunit-rrp6-in-saccharomyces-cerevisiae
#14
Fernando A Gonzales-Zubiate, Ellen K Okuda, Julia Pc Da Cunha, Carla Columbano Oliveira
The exosome is a conserved multiprotein complex essential for RNA processing and degradation. The nuclear exosome is a key factor for pre-rRNA processing through the activity of its catalytic subunits, Rrp6 and Rrp44. In Saccharomyces cerevisiae, Rrp6 is exclusively nuclear and has been shown to interact with exosome cofactors. With the aim of analyzing proteins associated with the nuclear exosome, in this work, we purified the complex with Rrp6-TAP, identified the co-purified proteins by mass spectrometry, and found karyopherins to be one of the major groups of proteins enriched in the samples...
May 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28539359/a-transcription-factor-iia-binding-site-differentially-regulates-rna-polymerase-ii-mediated-transcription-in-a-promoter-context-dependent-manner
#15
Juan Wang, Shasha Zhao, Wei He, Yun Wei, Yang Zhang, Henry Pegg, Paul Shore, Stefan Ge Roberts, Wensheng Deng
RNA polymerase II polymerase II (pol II) is required for the transcription of all protein-coding genes and as such represents a major enzyme whose activity is tightly regulated. Transcriptional initiation therefore requires numerous general transcriptional factors and cofactors that associate with pol II at core promoter to form a pre-initiation complex. Transcription factor IIA (TFIIA) is a general cofactor that binds TFIID and stabilizes the TFIID-DNA complex during transcription initiation. Previous studies showed that TFIIA can make contact with the DNA sequence upstream or downstream of the TATA-box, and that the region bound by TFIIA could overlap with the elements recognized by another factor, TFIIB, at adenovirus major late core promoter...
May 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28539183/measurement-of-intraocular-pressure-in-healthy-anesthetized-horses-during-hoisting
#16
Caroline S Monk, Dennis E Brooks, Tiffany Granone, Fernando L Garcia-Pereira, Alexander Melesko, Caryn E Plummer
OBJECTIVE: To measure intraocular pressure (IOP) in horses during hoisting after induction of anesthesia. STUDY DESIGN: Prospective nonrandomized clinical study. ANIMALS: Eighteen healthy adult horses aged [mean±standard deviation (SD)] 10±4.2 years and weighing 491±110 kg anesthetized for elective procedures. METHODS: IOP was measured in the superior eye of each horse based on planned recumbency after induction of anesthesia...
January 11, 2017: Veterinary Anaesthesia and Analgesia
https://www.readbyqxmd.com/read/28539047/identifying-the-protein-interactions-of-the-cytosolic-iron-sulfur-cluster-targeting-complex-essential-for-its-assembly-and-recognition-of-apo-targets
#17
Amanda Thuy Van Vo, Nicholas M Fleischman, Mary J Froehlich, Claudia Y Lee, Jessica A Cosman, Calina A Glynn, Zanub O Hassan, Deborah L Perlstein
The cytosolic iron sulfur cluster assembly (CIA) system assembles iron sulfur (FeS) cluster cofactors and inserts them into >20 apo-protein targets residing in the cytosol and nucleus. Three CIA proteins, called Cia1, Cia2, and Met18 in yeast, form the targeting complex responsible for apo-target recognition. There is little information about the structure of this complex or its mechanism of CIA substrate recognition. Herein, we exploit affinity co-purification and size exclusion chromatography to determine the subunit connectivity and stoichiometry of the CIA targeting complex...
May 25, 2017: Biochemistry
https://www.readbyqxmd.com/read/28538514/long-term-outcome-of-4-patients-with-transcobalamin-deficiency-caused-by-2-novel-tcn2-mutations
#18
Marwan Nashabat, Gustavo Maegawa, Peter H Nissen, Ebba Nexo, Hussain Al-Shamrani, Mohammed Al-Owain, Majid Alfadhel
Cobalamin (vitamin B12 [Cbl]) is an essential cofactor for many biochemical pathways. Transcobalamin (TC) is required to internalize Cbl into the cells through membrane receptor-mediated endocytosis. Cbl is then processed in the cytoplasm and mitochondria by complementation factors leading to its active metabolites; methylcobalamin and 5-deoxyadenosyl-cobalamin. Deficiency of TC results in an elevation in methylmalonic acid and homocysteine. Patients usually present with macrocytic anemia, pancytopenia, failure to thrive, gastrointestinal symptoms, and neurological dysfunction...
May 22, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28538096/location-of-the-substrate-binding-site-of-the-cytochrome-bo3-ubiquinol-oxidase-from-escherichia-coli
#19
Sylvia K Choi, Lici Schurig-Briccio, Ziqiao Ding, Sangjin Hong, Chang Sun, Robert B Gennis
Cytochrome bo3 is a respiratory proton-pumping oxygen reductase that is a member of the heme-copper superfamily that utilizes ubiquinol-8 (Q8H2) as a substrate. The current consensus model has Q8H2 oxidized at a low affinity site (QL), passing electrons to a tightly bound quinone cofactor at a high affinity site (QH site) that stabilizes the one-electron reduced ubisemiquinone, facilitating the transfer of electrons to the redox active metal centers where O2 is reduced to water. The current work shows that the Q8 bound to the QH site is more dynamic than previously thought...
May 24, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28537421/glutathione-glutaredoxins-and-iron
#20
Carsten Berndt, Christopher Horst Lillig
SIGNIFICANCE: Glutathione is the most abundant cellular low molecular weight thiol in the majority of organisms in all kingdoms of life. Therefore, functions of glutathione and disturbed regulation of its concentration are associated with numerous physiological and pathological situations. Recent advances: The function of glutathione as redox buffer or antioxidant is increasingly being questioned. New functions, especially functions connected to the cellular iron homeostasis were elucidated...
May 24, 2017: Antioxidants & Redox Signaling
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