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D-amino acid oxidase

Vinita Jagannath, Miriam Gerstenberg, Christoph U Correll, Susanne Walitza, Edna Grünblatt
The glutamate hypothesis of schizophrenia is related to the proposed dysregulation of D-amino acid oxidase (DAO), DAO activator (DAOA)/G72, and Neuregulin 1 (NRG1) genes. Genetic studies have shown significant associations between DAO, DAOA, NRG1 single-nucleotide polymorphisms (SNPs), and schizophrenia. The systematic literature search yielded 6, 5, and 18 new studies for DAO, DAOA, and NRG1 published after 2011 and not included in the previous SchizophreniaGene (SZGene) meta-analysis. We conducted meta-analyses of 20, 23, and 48 case-control studies, respectively, to comprehensively evaluate the association of 8 DAO, 12 DAOA, and 14 NRG1 SNPs with schizophrenia...
September 1, 2017: Journal of Neural Transmission
Rizvan Uluisik, Elvira Romero, Giovanni Gadda
The effect of temperature on the reaction of alcohol oxidation catalyzed by choline oxidase was investigated with the S101A variant of choline oxidase. Anaerobic enzyme reduction in a stopped-flow spectrophotometer was biphasic using either choline or 1,2-[(2)H4]-choline as a substrate. The limiting rate constants klim1 and klim2 at saturating substrate were well separated (klim1/klim2>9), and were >15-fold slower than for wild-type choline oxidase. Solvent deuterium kinetic isotope effects (KIEs) ~4 established that klim1 probes the proton transfer from the substrate hydroxyl to a catalytic base...
August 24, 2017: Biochimica et Biophysica Acta
D Zappi, R Caminiti, G M Ingo, C Sadun, C Tortolini, M L Antonelli
Main purpose of the work is assembling, testing and optimizing new disposable amperometric biosensors to analyze substances in different application fields as agribusiness, clinical chemistry and environment protection. Many kinds of modified electrodes have been prepared and tested to build portable devices to analyze quickly many analytes, in a simple and cost-effective manner. Bare electrodes of the screen-printed type, with silver as reference, have been used for modification. The glassy carbon electrodes with multi-walled carbon nanotubes or graphene or gold nanoparticles depositions were modified with generation IV ionic liquids...
December 1, 2017: Talanta
Weiyu Wang, Jiaqi Sun, Wenjun Xiao, Li Jiang, Ruyue Wang, Jun Fan
OBJECTIVES: To optimize the production of active inclusion bodies (IBs) containing human D-amino acid oxidase (hDAAO) in Escherichia coli. RESULTS: The optimized initial codon region combined with the coexpressed rare tRNAs, fusion of each of the N-terminal partners including cellulose-binding module, thioredoxin, glutathione S-transferase and expressivity tag, deletion of the incorporated linker, and improvement of tRNA abundance affected the production and activity for oxidizing D-alanine of the hDAAO in IBs...
August 23, 2017: Biotechnology Letters
Qi Kuang, Sheng Zhang, Pingzhi Wu, Yaping Chen, Meiru Li, Huawu Jiang, Guojiang Wu
Jatropha curcas L. is an important biofuel plant with excellent tolerance of barren environments. However, studies on the regulatory mechanisms that operate in this plant in response to nitrogen (N) shortage are scarce. In this study, genome-wide transcriptional profiles of the roots and leaves of 8-week old physic nut seedlings were analyzed after 2 and 16 days of N starvation. Enrichment results showed that genes associated with N metabolism, processing and regulation of RNA, and transport predominated among those showing alterations in expression...
2017: PloS One
Gianluca Molla, Roberta Melis, Loredano Pollegioni
Enantiomerically pure amino acids are of increasing interest for the fine chemical, agrochemicals and pharmaceutical industries. During past years l-amino acids have been produced from deracemization of dl-solution employing the stereoselective flavoenzyme d-amino acid oxidase. On the other hand, the isolation of corresponding d-isomer was hampered by the scarce availability of a suitable l-amino acid oxidase activity. On this side, l-amino acid deaminase (LAAD), only present in the Proteus bacteria, represents a suitable alternative...
November 1, 2017: Biotechnology Advances
Eimear Howley, Michael Bestwick, Rosa Fradley, Helen Harrison, Mathew Leveridge, Kengo Okada, Charlotte Fieldhouse, Will Farnaby, Hannah Canning, Andy P Sykes, Kevin Merchant, Katherine Hazel, Catrina Kerr, Natasha Kinsella, Louise Walsh, David G Livermore, Isaac Hoffman, Jonathan Ellery, Phillip Mitchell, Toshal Patel, Mark Carlton, Matt Barnes, David J Miller
Irregular N-methyl-D-aspartate receptor (NMDAR) function is one of the main hypotheses employed to facilitate understanding of the underlying disease state of schizophrenia. Although direct agonism of the NMDAR has not yielded promising therapeutics, advances have been made by modulating the NMDAR co-agonist site which is activated by glycine and D-serine. One approach to activate the co-agonist site is to increase synaptic D-serine levels through inhibition of D-amino acid oxidase (DAO), the major catabolic clearance pathway for this and other D-amino acids...
August 5, 2017: Neurochemical Research
Cleverson D T Freitas, Deborah C Freitas, Wallace T Cruz, Camila T M N Porfírio, Maria Z R Silva, Jefferson S Oliveira, Cristina Paiva S Carvalho, Márcio V Ramos
Germin-like proteins (GLPs) have been identified in several plant tissues. However, only one work describes GLP in latex fluids. Therefore, the goal of this study was to investigate GLPs in latex and get new insights concerning the structural and functional aspects of these proteins. Two complete sequences with high identity (>50%) with other GLPs, termed CpGLP1 and CpGLP2, were obtained and consecutively presented 216 and 206 amino acid residues, corresponding to molecular masses of 22.7 and 21.7kDa, pI 6...
July 25, 2017: International Journal of Biological Macromolecules
Brwa Rasool, Jack McGowan, Daria Pastok, Sue E Marcus, Jenny A Morris, Susan R Verrall, Peter E Hedley, Robert D Hancock, Christine H Foyer
The mechanisms underpinning plant perception of phloem-feeding insects, particularly aphids, remain poorly characterized. Therefore, the role of apoplastic redox state in controlling aphid infestation was explored using transgenic tobacco (Nicotiana tabacum) plants that have either high (PAO) or low (TAO) ascorbate oxidase (AO) activities relative to the wild type. Only a small number of leaf transcripts and metabolites were changed in response to genotype, and cell wall composition was largely unaffected. Aphid fecundity was decreased significantly in TAO plants compared with other lines...
September 2017: Plant Physiology
Biswajit Bose, Hiranjit Choudhury, Pramod Tandon, Suman Kumaria
Malaxis acuminata D. Don., a small, terrestrial orchid, is endemic to tropical Himalayas at an altitude of 1200-2000m asl. The dried pseudobulbs are important ingredients of century old ayurvedic drug 'Ashtavarga' and a polyherbal immune-booster nutraceutical 'Chyavanprash', known to restore vigour, vitality and youthfulness. Considering tremendous medicinal importance of this threatened orchid species, a detailed study was undertaken for the first time to address its antioxidant potential, secondary metabolite contents and biological activities against skin-aging related enzymes (anti-collagenase, anti-elastase, anti-tyrosinase and xanthine oxidase) and anti-inflammatory activity (5-lipoxygenase and hyaluronidase) in different plant parts of wild and in vitro-derived plants of M...
August 2017: Journal of Photochemistry and Photobiology. B, Biology
Junxian Zheng, Taowei Yang, Junping Zhou, Meijuan Xu, Xian Zhang, Zhiming Rao, Shangtian Yang
Native d-amino acid oxidase (DAAO) that is expressed mostly as inclusion body and its toxicity for E. coli hamper efficient heterologous expression. In this study, the soluble expression of DAAO from Rhodosporidium toruloides (RtDAAO) was improved in E. coli through N-terminal modification, but the cell biomass was decreased. Then a trade-off between DAAO expression and biomass was achieved to obtain the highest volumetric activity of DAAO through regulated the number of N-terminus histidine residues. When variant (2)H(3)G was fused with three N-terminus histidine residues, the volumetric activity was increased by 3...
July 5, 2017: Bioresource Technology
Carmen Chow, Subray Hegde, John S Blanchard
l-Aspartate oxidase, encoded by the nadB gene, is the first enzyme in the de novo synthesis of NAD(+) in bacteria. This FAD-dependent enzyme catalyzes the oxidation of l-aspartate to generate iminoaspartate and reduced flavin. Distinct from most amino acid oxidases, it can use either molecular oxygen or fumarate to reoxidize the reduced enzyme. Sequence alignments and the three-dimensional crystal structure have revealed that the overall fold and catalytic residues of NadB closely resemble those of the succinate dehydrogenase/fumarate reductase family rather than those of the prototypical d-amino acid oxidases...
August 8, 2017: Biochemistry
Giuseppe Genchi
More than half a century ago researchers thought that D-amino acids had a minor function compared to L-enantiomers in biological processes. Many evidences have shown that D-amino acids are present in high concentration in microorganisms, plants, mammals and humans and fulfil specific biological functions. In the brain of mammals, D-serine (D-Ser) acts as a co-agonist of the N-methyl-D-aspartate (NMDA)-type glutamate receptors, responsible for learning, memory and behaviour. D-Ser metabolism is relevant for disorders associated with an altered function of the NMDA receptor, such as schizophrenia, ischemia, epilepsy and neurodegenerative disorders...
July 5, 2017: Amino Acids
Saki Shimizu, Shunsaku Sogabe, Ryoto Yanagisako, Akiyoshi Inada, Megumi Yamanaka, Higor A Iha, Yukihiro Ohno
Dysfunction of the N-methyl-d-aspartate (NMDA) receptor has been implicated in the pathogenesis of schizophrenia. Although agonists for the glycine-binding sites of NMDA receptors have potential as new medication for schizophrenia, their modulation of antipsychotic-induced extrapyramidal side effects (EPS) has not yet been clarified. We herein evaluated the effects of glycine-binding site stimulants of NMDA receptors on antipsychotic-induced EPS in mice and rats. d-cycloserine (DCS) and d-serine significantly improved haloperidol (HAL)-induced bradykinesia in mice, whereas glycine showed no effects...
July 3, 2017: International Journal of Molecular Sciences
Kiattisak Lugsanangarm, Arthit Nueangaudom, Somsak Pianwanit, Sirirat Kokpol, Nadtanet Nunthaboot, Fumio Tanaka, Seiji Taniguchi, Haik Chosrowjan
Pyranose 2-oxidase (P2O) from Trametes multicolor contains FAD as cofactor, and forms a tetramer. The protein structure of a mutated P2O, T169S (Thr169 is replaced by Ser), in solution was studied by means of molecular dynamics simulation and analyses of photoinduced electron transfer (ET) from Trp168 to excited isoalloxazine (Iso*), and was compared with wild type (WT) P2O. Hydrogen bonding between Iso and nearby amino acids was very similar as between T169S and WT protein. Distances between Iso and Tyr456 were extremely heterogeneous among the subunits, 1...
July 2, 2017: Proteins
Masumi Katane, Ryo Kanazawa, Risa Kobayashi, Megumi Oishi, Kazuki Nakayama, Yasuaki Saitoh, Tetsuya Miyamoto, Masae Sekine, Hiroshi Homma
d-Aspartate oxidase (DDO) is a degradative enzyme that is stereospecific for the acidic amino acid d-aspartate, an endogenous agonist of the N-methyl-d-aspartate (NMDA) receptor. Dysregulation of NMDA receptor-mediated neurotransmission has been implicated in the onset of various neuropsychiatric disorders including schizophrenia and in chronic pain. Thus, appropriate regulation of the amount of d-aspartate is believed to be important for maintaining proper neural activity in the nervous system. Herein, the effects of the non-synonymous single nucleotide polymorphisms (SNPs) R216Q and S308N on several properties of human DDO were examined...
September 2017: Biochimica et Biophysica Acta
Yulia A Bogdanova, Carsten Schultz, Vsevolod V Belousov
Described here is a localized H2 O2 generation-detection system consisting of a yeast D-amino acid oxidase (DAAO) and two spectrally distinct variants of biosensor, HyPer2 and HyPerRed based on circularly permutated yellow and red fluorescent proteins, respectively, which enables spatiotemporal production and examination of the intracellular H2 O2 dynamics. The protocol describes using this system in a simple cell culture model. We provide detailed instructions on imaging of H2 O2 generated by the activated DAAO...
June 19, 2017: Current Protocols in Chemical Biology
Ayse Nalbantsoy, Benjamin-Florian Hempel, Daniel Petras, Paul Heiss, Bayram Göçmen, Nasit Iğci, Mehmet Zülfü Yildiz, Roderich D Süssmuth
Here we report the first characterization of the endemic Mount Bulgar Viper (Montivipera bulgardaghica) and Radde's mountain viper (Montivipera raddei) venom by a combined approach using intact mass profiling and bottom-up proteomics. The cytotoxicity screening of crude venom as well as isolated serine proteases revealed a high activity against A549 human lung carcinoma cells. By means of intact mass profiling of native and reduced venom we observed basic and acidic phospholipases type A2. Moreover, the analysis revealed snake venom metalloproteases, cysteine-rich secretory proteins, disintegrins, snake venom serine proteases, C-type lectins, a vascular endothelial growth factor and an L-amino acid oxidase...
June 16, 2017: Toxicon: Official Journal of the International Society on Toxinology
Peter Hahl, Rachel Hunt, Edward S Bjes, Andrew Skaff, Andrew Keightley, Ann Smith
Hemopexin protects against heme toxicity in hemolytic diseases and conditions, sepsis, and sickle cell disease. This protection is sustained by heme-hemopexin complexes in biological fluids that resist oxidative damage during heme-driven inflammation. However, apo-hemopexin is vulnerable to inactivation by reactive nitrogen (RNS) and oxygen species (ROS) that covalently modify amino acids. The resultant nitration of amino acids is considered a specific effect reflecting biological events. Using LC-MS, we discovered low endogenous levels of tyrosine nitration in the peptide YYCFQGNQFLR in the heme-binding site of human hemopexin, which was similarly nitrated in rabbit and rat hemopexins...
August 18, 2017: Journal of Biological Chemistry
Qingju Liu, Li Chen, Zhikun Zhang, Bibai Du, Yating Xiao, Kunhao Yang, Lingling Gong, Li Wu, Xiangjun Li, Yujian He
D-amino acid oxidases (DAAO) are stereospecific enzymes which are generally almost inactive towards L-enantiomer in neutral solution when L-, D-amino acids are supplied as substrates. In this paper, the D-amino acid oxidase can catalytic oxidize L-amino acids by modulating pH of aqueous solution. With L-Pro as substrate, the catalytic rate (k cat) and the affinity (K m) of DAAO were 6.71 s(-1) and 33 mM at pH 8.0, respectively, suggesting that optimal pH condition enhanced the activity of DAAO towards L-Pro...
June 7, 2017: Scientific Reports
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