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https://www.readbyqxmd.com/read/30550897/uridine-diphosphate-release-mechanism-in-o-n-acetylglucosamine-o-glcnac-transferase-catalysis
#1
Nai She, Yuan Zhao, Jingjing Hao, Songqiang Xie, Chaojie Wang
O-linked N-acetylglucosamine transferase (OGT) is an essential enzyme that catalyzes the covalent bonding of N-acetylglucosamine (GlcNAc) to the hydroxyl group of a serine or threonine in the target protein. It plays an important role in many important cellular physiological catalytic reactions. Here, we determine the binding mode and the binding free energy of the OGT product (uridine diphosphate, UDP) as well as the hydrogen-bond-dependent release mechanism using extensive molecular dynamic simulations. The Lys634, Asn838, Gln839, Lys842, His901, and Asp925 residues were identified to play a major role in the UDP stabilization in the active site of OGT, where hydrogen bonding and π-π interactions mainly occur...
December 11, 2018: Biochimica et biophysica acta. General subjects
https://www.readbyqxmd.com/read/30550731/a-novel-catalase-mimicking-nanocomposite-of-mn-ii-poly-l-histidine-carboxylated-multi-walled-carbon-nanotubes-and-the-application-to-hydrogen-peroxide-sensing
#2
Jiexin Zhou, Yuan Chen, Lintao Lan, Cong Zhang, Meixin Pan, Yingying Wang, Bingkai Han, Zihua Wang, Jun Jiao, Qiang Chen
In this work, a novel enzyme-mimicking nanocomposite of Mn(II)-poly-L-histidine (PLH) functionalized carboxylated multi walled carbon nanotubes (CMWCNTs) was designed and synthesized. Based on the catalase-like activity of the nanocomposite, a non-enzymatic hydrogen peroxide (H2O2) biosensor was then established and explored for H2O2 electrochemical detection. The nanocomposite was characterized by Fourier transform infrared spectra, Raman spectroscopy, and transmission electron microscopy. Due to the enlarged effective surface area and the efficient electrocatalytic activity of the Mn(II)-PLH redox-active units, the obtained Mn(II)-PLH-CMWCNT electrode showed excellent electrocatalytic performance toward H2O2 disproportionation...
December 11, 2018: Analytical Biochemistry
https://www.readbyqxmd.com/read/30550726/the-cytochrome-b-lysine-329-residue-is-critical-for-ubihydroquinone-oxidation-and-proton-release-at-the-q-o-site-of-bacterial-cytochrome-bc-1
#3
Francesco Francia, Bahia Khalfaoui-Hassani, Pascal Lanciano, Francesco Musiani, Louis Noodleman, Giovanni Venturoli, Fevzi Daldal
The ubihydroquinone:cytochrome (cyt) c oxidoreductase (or cyt bc1 ) is an important enzyme for photosynthesis and respiration. In bacteria like Rhodobacter capsulatus, this membrane complex has three subunits, the iron‑sulfur protein (ISP) with its Fe2 S2 cluster, cyt c1 and cyt b, forming two catalytic domains, the Qo (hydroquinone (QH2 ) oxidation) and Qi (quinone (Q) reduction) sites. At the Qo site, the electron transfer pathways originating from QH2 oxidation are known, but their associated proton release routes are less well defined...
December 11, 2018: Biochimica et biophysica acta. Bioenergetics
https://www.readbyqxmd.com/read/30548600/defining-the-complement-c3-binding-site-and-the-antigenic-region-of-haemonchus-contortus-gapdh
#4
Parvathy Rajan, Prasanta K K Mishra, Paritosh Joshi
Haemonchus contortus is an economically important parasite that survives the host defense system by modulating the immune response. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is secreted by the parasite and the host responds by producing anti-enzyme antibodies. The enzyme inhibits complement cascade, an arm of the innate immunity, by binding to complement C3. In this study, the C3 binding site and the antigenic region of the enzyme were identified by generating short recombinant fragments and deleting a defined region of the enzyme...
December 12, 2018: Parasite Immunology
https://www.readbyqxmd.com/read/30546968/fatigued-patients-with-chronic-liver-disease-have-subtle-aberrations-of-sleep-melatonin-and-cortisol-circadian-rhythms
#5
Michele M Tana, Hawwa Alao, Nevitt Morris, Shanna Bernstein, Jacob Hattenbach, Rahiya B Rehman, Robert Brychta, Souvik Sarkar, Xiongce Zhao, Mary Walter, Ashura Buckley, Kong Chen, Yaron Rotman
Aims: We sought to examine whether disturbances in central and peripheral circadian rhythms were related to the experience of fatigue in patients with chronic liver disease (CLD). Methods: Fatigued and non-fatigued patients with compensated CLD were enrolled in a prospective pilot study. Patients underwent a one week evaluation of free-living sleep and physical activity patterns, followed by a 24-hour admission, during which they underwent serial blood sampling, polysomnography, a 6-minute walk test and continuous core temperature measurements under standardized conditions...
2018: Fatigue: Biomedicine, Health and Behavior
https://www.readbyqxmd.com/read/30546837/anticancer-activity-of-2-hydroxyflavanone-towards-lung-cancer
#6
Sanjay Awasthi, Sharad S Singhal, Jyotsana Singhal, Lokesh Nagaprashantha, Hongzhi Li, Yate-Ching Yuan, Zheng Liu, David Berz, Henry Igid, William C Green, Lukman Tijani, Vijay Tonk, Aditya Rajan, Yogesh Awasthi, Sharda P Singh
In previous studies, we found that 2'-hydroxyflavonone (2HF), a citrus flavonoid, inhibits the growth of renal cell carcinoma in a VHL-dependent manner. This was associated with the inhibition of glutathione S-transferases (GSTs), the first step enzyme of the mercapturic acid pathway that catalyzes formation of glutathione-electrophile conjugates (GS-E). We studied 2HF in small cell (SCLC) and non-small cell (NSCLC) lung cancer cell lines for sensitivity to 2HF antineoplastic activity and to determine the role of the GS-E transporter Rlip (Ral-interacting protein; RLIP76; RALBP1) in the mechanism of action of 2HF...
November 16, 2018: Oncotarget
https://www.readbyqxmd.com/read/30546390/exenatide-reduces-oxidative-stress-and-cell-death-in-testis-in-iron-overload-rat-model
#7
Suleyman Yesil, Nuran Sungu, Aydan Kilicarslan, Serife Mehlika Kuskonmaz, Halil Kara, Aysegul Kucuk, Fazli Polat, Mustafa Kavutcu, Mustafa Arslan
Glucagon-like peptide-1 (GLP-1) has been demonstrated to affect the oxidative stress status in several in vitro, in vivo and clinical studies. The aim of the present study was to evaluate the effect of a GLP-1 analogue, exenatide, on oxidative stress parameters and apoptotic markers in testicular cells in an iron overload rat model. To obtain this model, the animals were randomly divided into three groups (n=6/group). Rats in the control group received intraperitoneal injections of saline. Intraperitoneal iron dextran (60 mg/kg/day) was given to Group FE for 5 days a week for 4 weeks...
December 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/30546256/peripheral-biomarker-for-vascular-disorders
#8
Kaneez Fatima Shad, Nazar Luqman, Ann M Simpson, Sara Lal
Atherosclerosis is the underlying cause of most myocardial infarction (MI) and ischaemic stroke episodes. An early sign of atherosclerosis is hypertrophy of the arterial wall. It is known that increased intima media thickness (IMT) is a non-invasive marker of arterial wall alteration, which can easily be assessed in the carotid arteries by high-resolution B-mode ultrasound. Similarly, the other key element of MI and ischaemic strokes is the N-methyl-D-aspartate (NMDA) receptor which is an ionotropic glutamate receptor that mediates the vast majority of excitatory neurotransmission in the brain...
2018: Biomarker Insights
https://www.readbyqxmd.com/read/30545937/cholesterol-increases-protein-levels-of-the-e3-ligase-march6-and-thereby-stimulates-protein-degradation
#9
Laura J Sharpe, Vicky Howe, Nicola A Scott, Winnie Luu, Lisa Phan, Jason M Berk, Mark Hochstrasser, Andrew J Brown
The E3 ligase membrane-associated ring-CH-type finger 6 (MARCH6) is a polytopic enzyme bound to the membranes of the endoplasmic reticulum. It controls levels of several known protein substrates, including a key enzyme in cholesterol synthesis, squalene monooxygenase. However, beyond its own autodegradation, little is known about how MARCH6 itself is regulated. Using CRISPR/Cas9 gene-editing, MARCH6 overexpression, and immunoblotting, we found here that cholesterol stabilizes MARCH6 protein endogenously and in HEK293 cells that stably express MARCH6...
December 13, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/30545741/insulin-like-growth-factor-1-activates-ampk-to-augment-mitochondrial-function-and-correct-neuronal-metabolism-in-sensory-neurons-in-type-1-diabetes
#10
Mohamad-Reza Aghanoori, Darrell R Smith, Shiva Shariati-Ievari, Andrew Ajisebutu, Annee Nguyen, Fiona Desmond, Carlos H A Jesus, Xiajun Zhou, Nigel A Calcutt, Michel Aliani, Paul Fernyhough
OBJECTIVE: Diabetic sensorimotor polyneuropathy (DSPN) affects approximately half of diabetic patients leading to significant morbidity. There is impaired neurotrophic growth factor signaling, AMP-activated protein kinase (AMPK) activity and mitochondrial function in dorsal root ganglia (DRG) of animal models of type 1 and type 2 diabetes. We hypothesized that sub-optimal insulin-like growth factor 1 (IGF-1) signaling in diabetes drives loss of AMPK activity and mitochondrial function, both contributing to development of DSPN...
November 28, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/30544979/proteomics-analysis-reveals-that-caspase-like-and-metacaspase-like-activities-are-dispensable-for-activation-of-proteases-involved-in-early-response-to-biotic-stress-in-triticum-aestivum-l
#11
Anastasia V Balakireva, Andrei A Deviatkin, Victor G Zgoda, Maxim I Kartashov, Natalia S Zhemchuzhina, Vitaly G Dzhavakhiya, Andrey V Golovin, Andrey A Zamyatnin
Plants, including Triticum aestivum L., are constantly attacked by various pathogens which induce immune responses. Immune processes in plants are tightly regulated by proteases from different families within their degradome. In this study, a wheat degradome was characterized. Using profile hidden Markov model (HMMer) algorithm and Pfam database, comprehensive analysis of the T. aestivum genome revealed a large number of proteases (1544 in total) belonging to the five major protease families: serine, cysteine, threonine, aspartic, and metallo-proteases...
December 11, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/30544642/acceptor-stem-differences-contribute-to-species-specific-use-of-yeast-and-human-trna-ser
#12
Matthew D Berg, Julie Genereaux, Yanrui Zhu, Safee Mian, Gregory B Gloor, Christopher J Brandl
The molecular mechanisms of translation are highly conserved in all organisms indicative of a single evolutionary origin. This includes the molecular interactions of tRNAs with their cognate aminoacyl-tRNA synthetase, which must be precise to ensure the specificity of the process. For many tRNAs, the anticodon is a major component of the specificity. This is not the case for the aminoacylation of alanine and serine to their cognate tRNAs. Rather, aminoacylation relies on other features of the tRNA. For tRNASer , a key specificity feature is the variable arm, which is positioned between the anticodon arm and the T-arm...
December 7, 2018: Genes
https://www.readbyqxmd.com/read/30544606/biosynthesis-and-secretion-of-human-tissue-kallikrein-in-transgenic-chlamydomonas-reinhardtii
#13
Jun Chen, Jinxia Wu, Qingyu Wu, Zhangli Hu
The green alga Chlamydomonas reinhardtii was recently been shown to be an effective bio-manufacturing platform for the production of recombinant proteins. The advantage of using C. reinhardtii is that it is fast to grow, inexpensive to culture, and relatively safe. However, the expression of foreign proteins is always low and difficult to purify in C. reinhardtii . Human kallikrein has the potential to be developed into certain drugs, like insulin. Therefore, its biosynthesis is important to drug development...
December 7, 2018: Marine Drugs
https://www.readbyqxmd.com/read/30544151/lateral-gene-transfer-shapes-the-distribution-of-rubisco-among-candidate-phyla-radiation-bacteria-and-dpann-archaea
#14
Alexander L Jaffe, Cindy J Castelle, Christopher L Dupont, Jillian F Banfield
Ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) is considered to be the most abundant enzyme on Earth. Despite this, its full diversity and distribution across the domains of life remain to be determined. Here, we leverage a large set of bacterial, archaeal, and viral genomes recovered from the environment to expand our understanding of existing RuBisCO diversity and the evolutionary processes responsible for its distribution. Specifically, we report a new type of RuBisCO present in Candidate Phyla Radiation (CPR) bacteria that is related to the archaeal Form III enzyme and contains the amino acid residues necessary for carboxylase activity...
December 13, 2018: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/30544060/a-cost-analysis-of-upfront-dpyd-genotype-guided-dose-individualisation-in-fluoropyrimidine-based-anticancer-therapy
#15
Linda M Henricks, Carin A T C Lunenburg, Femke M de Man, Didier Meulendijks, Geert W J Frederix, Emma Kienhuis, Geert-Jan Creemers, Arnold Baars, Vincent O Dezentjé, Alexander L T Imholz, Frank J F Jeurissen, Johanna E A Portielje, Rob L H Jansen, Paul Hamberg, Albert J Ten Tije, Helga J Droogendijk, Miriam Koopman, Peter Nieboer, Marlène H W van de Poel, Caroline M P W Mandigers, Hilde Rosing, Jos H Beijnen, Erik van Werkhoven, André B P van Kuilenburg, Ron H N van Schaik, Ron H J Mathijssen, Jesse J Swen, Hans Gelderblom, Annemieke Cats, Henk-Jan Guchelaar, Jan H M Schellens
BACKGROUND: Fluoropyrimidine therapy including capecitabine or 5-fluorouracil can result in severe treatment-related toxicity in up to 30% of patients. Toxicity is often related to reduced activity of dihydropyrimidine dehydrogenase, the main metabolic fluoropyrimidine enzyme, primarily caused by genetic DPYD polymorphisms. In a large prospective study, it was concluded that upfront DPYD-guided dose individualisation is able to improve safety of fluoropyrimidine-based therapy. In our current analysis, we evaluated whether this strategy is cost saving...
December 10, 2018: European Journal of Cancer
https://www.readbyqxmd.com/read/30543953/response-of-bloom-forming-cyanobacterium-microcystis-aeruginosa-to-17%C3%AE-estradiol-at-different-nitrogen-levels
#16
Leilei Bai, Chicheng Cao, Changhui Wang, Hui Zhang, Jiancai Deng, Helong Jiang
Co-existence of cyanobacterial harmful algal blooms (CyanoHABs) and steroid estrogens (SEs) has been an increasing concern in eutrophic waters. The cellular responses and biodegradation of 17β-estradiol (E2) in cyanobacterium Microcystis aeruginosa were investigated at different nitrogen levels. During the 10-d experiment, the growth of M. aeruginosa was stimulated by 10-100 μg L-1 of E2 at the lowest nitrogen level of 0.5 mg L-1 , whereas the presence of E2 inhibited the cyanobacterial growth at 5 mg L-1 of nitrogen...
December 1, 2018: Chemosphere
https://www.readbyqxmd.com/read/30543776/o-glcnac-transferase-links-glucose-metabolism-to-mavs-mediated-antiviral-innate-immunity
#17
Tianliang Li, Xinghui Li, Kuldeep S Attri, Changhong Liu, Lupeng Li, Laura E Herring, John M Asara, Yu L Lei, Pankaj K Singh, Chengjiang Gao, Haitao Wen
Increased glucose metabolism in immune cells not only serves as a hallmark feature of acute inflammation but also profoundly affects disease outcome following bacterial infection and tissue damage. However, the role of individual glucose metabolic pathways during viral infection remains largely unknown. Here we demonstrate an essential function of the hexosamine biosynthesis pathway (HBP)-associated O-linked β-N-acetylglucosamine (O-GlcNAc) signaling in promoting antiviral innate immunity. Challenge of macrophages with vesicular stomatitis viruses (VSVs) enhances HBP activity and downstream protein O-GlcNAcylation...
December 12, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/30543682/developmental-and-tissue-specific-changes-of-ubiquitin-forms-in-drosophila-melanogaster
#18
Ágota Nagy, Levente Kovács, Zoltán Lipinszki, Margit Pál, Péter Deák
In most Eukaryotes, ubiquitin either exists as free monoubiquitin or as a molecule that is covalently linked to other proteins. These two forms cycle between each other and due to the concerted antagonistic activity of ubiquitylating and deubiquitylating enzymes, an intracellular ubiquitin equilibrium is maintained that is essential for normal biological function. However, measuring the level and ratio of these forms of ubiquitin has been difficult and time consuming. In this paper, we have adapted a simple immunoblotting technique to monitor ubiquitin content and equilibrium dynamics in different developmental stages and tissues of Drosophila...
2018: PloS One
https://www.readbyqxmd.com/read/30543165/unlocking-the-potential-of-hk2-in-cancer-metabolism-and-therapeutics
#19
Sara N Garcia, Rita C Guedes, M Matilde Marques
Glycolysis is a tightly regulated process in which several enzymes, such as hexokinases (HKs), play crucial roles. Cancer cells are characterized by specific expression levels of several isoenzymes in different metabolic pathways and these fea-tures offer possibilities for therapeutic interventions. Overexpression of HKs (mostly of the HK2 isoform) has been con-sistently reported in numerous types of cancer. Moreover, deletion of HK2 has been shown to decrease cancer cell prolif-eration without explicit side effects in animal models, which suggests that targeting HK2 is a viable strategy for cancer therapy...
December 12, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/30542517/pitfalls-on-sample-preparation-for-ex-vivo-imaging-of-resected-cancer-tissue-using-enzyme-activatable-fluorescent-probes
#20
Ai Mochida, Fusa Ogata, Yasuhiro Maruoka, Tadanobu Nagaya, Ryuhei Okada, Fuyuki Inagaki, Daiki Fujimura, Peter L Choyke, Hisataka Kobayashi
In vivo and ex vivo fluorescence imaging-assisted surgery can aid in determining the margins of tumors during surgical resection. While a variety of fluorescent probes have been proposed for this task, small molecule enzyme-activatable fluorescent probes are ideal for this application. They are quickly activated at tumor sites and result in bright signal with little background, resulting in high sensitivity. Testing in resected specimens, however, can be difficult. Enzymes are usually stable after freezing and thawing but catalytic reactions are generally temperature-dependent...
November 13, 2018: Oncotarget
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