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D-amino acid oxidase

Sarah Matthews, James D Belcher, Kang Lan Tee, Hazel M Girvan, Kirsty J McLean, Stephen Ej Rigby, Colin W Levy, David Leys, David A Parker, Richard T Blankley, Andrew W Munro
The Jeotgalicoccus sp. peroxygenase cytochrome P450 OleTJE (CYP152L1) is a hydrogen peroxide-driven oxidase that catalyzes oxidative decarboxylation of fatty acids, producing terminal alkenes with applications as fine chemicals and biofuels. Understanding mechanisms that favor decarboxylation over fatty acid hydroxylation in OleTJE could enable protein engineering to improve catalysis or to introduce decarboxylation activity into P450s with different substrate preferences. In this manuscript, we have focused on OleTJE active site residues Phe79, His85 and Arg245 to interrogate their roles in substrate binding and catalytic activity...
January 4, 2017: Journal of Biological Chemistry
Wan Wang, Weisong Duan, Ying Wang, Di Wen, Yakun Liu, Zhongyao Li, Haojie Hu, Hongying Cui, Can Cui, Huiqian Lin, Chunyan Li
Amyotrophic lateral sclerosis (ALS) is an adult-onset, irreversible neurodegenerative disease that leads to progressive paralysis and inevitable death 3-5 years after diagnosis. The mechanisms underlying this process remain unknown, but new evidence indicates that accumulating levels of D-serine result from the downregulation of D-amino acid oxidase (DAO) and that this is a novel mechanism that leads to motoneuronal death in ALS via N-methyl-D-aspartate receptor-mediated cell toxicity. Here, we explored a new therapeutic approach to ALS by overexpressing DAO in the lumbar region of the mouse spinal cord using a single stranded adeno-associated virus serotype 9 (ssAAV9) vector...
December 26, 2016: Neurochemical Research
Martin Kohlstaedt, Sabine Buschmann, Julian D Langer, Hao Xie, Hartmut Michel
The Cbb3-type cytochrome c oxidases (Cbb3-CcOs), the second most abundant CcOs, catalyze the reduction of molecular oxygen to water, even at micromolar oxygen concentrations. In Pseudomonas stutzeri ZoBell, two tandemly organized cbb3-operons encode the isoforms Cbb3-1 and Cbb3-2 both possessing subunits CcoN, CcoO and CcoP. However, only the cbb3-2 operon contains an additional ccoQ gene. CcoQ consists of 62 amino acids and is predicted to possess one transmembrane spanning helix. The physiological role of CcoQ was investigated based on a CcoQ-deletion mutant and wild-type Cbb3-2 crystals not containing subunit CcoQ...
December 20, 2016: Biochimica et Biophysica Acta
Daniel Francis, Michael Winn, Jonathan Latham, Michael F Greaney, Jason Micklefield
β-Methyltryptophans (β-mTrp) are precursors in the biosynthesis of bioactive natural products and are used in the synthesis of peptidomimetic based therapeutics. Currently β-mTrp is produced by inefficient multi-step synthetic methods. Here we demonstrate how an engineered variant of tryptophan synthase from Salmonella (StTrpS) can catalyse the efficient condensation of L-threonine and various indoles to generate β-mTrp and derivatives in a single step. Although L-serine is the natural substrate for TrpS, targeted mutagenesis of the StTrpS active site provided a variant (βL166V) which can better accommodate L-Thr as a substrate...
December 22, 2016: Chembiochem: a European Journal of Chemical Biology
HuiQian Lin, HaoJie Hu, WeiSong Duan, YaLing Liu, GuoJun Tan, ZhongYao Li, YaKun Liu, BinBin Deng, XueQin Song, Wan Wang, Di Wen, Ying Wang, ChunYan Li
Self-complementary adeno-associated viral vector 9 (scAAV9) has been confirmed to be an efficient AAV serotype for gene transfer to the central nervous system (CNS). Neurotrophic factors have been considered to be therapeutic targets for amyotrophic lateral sclerosis (ALS). In the present study, we intramuscularly injected scAAV9 encoding human insulin-like growth factor 1 (hIGF1) into an hSOD1(G93A) ALS mouse model. We observed that scAAV9-hIGF1 significantly reduced the loss of motor neurons of the anterior horn in the lumbar spinal cord and delayed muscle atrophy in ALS mice...
December 19, 2016: Molecular Neurobiology
Yusuke Kato, Kiyoshi Fukui
The G72 gene is one of the most susceptible genes to schizophrenia and is contained exclusively in the genomes of primates. The product of the G72 gene modulates the activity of D-amino acid oxidase (DAO) and is a small protein prone to aggregate, which hampers its structural studies. In addition, lack of a known structure of a homologue makes it difficult to use the homology modelling method for the prediction of the structure. Thus, we first developed a hybrid ab initio approach for small proteins prior to the prediction of the structure of G72...
November 3, 2016: Journal of Biochemistry
Xu Cao, Jin-Song Bian
Hydrogen sulfide has gained recognition as the third gaseous signaling molecule after nitric oxide and carbon monoxide. This review surveys the emerging role of H2S in mammalian renal system, with emphasis on both renal physiology and diseases. H2S is produced redundantly by four pathways in kidney, indicating the abundance of this gaseous molecule in the organ. In physiological conditions, H2S was found to regulate the excretory function of the kidney possibly by the inhibitory effect on sodium transporters on renal tubular cells...
2016: Frontiers in Pharmacology
Fernando J Martinez, Gabriel A Pratt, Eric L Van Nostrand, Ranjan Batra, Stephanie C Huelga, Katannya Kapeli, Peter Freese, Seung J Chun, Karen Ling, Chelsea Gelboin-Burkhart, Layla Fijany, Harrison C Wang, Julia K Nussbacher, Sara M Broski, Hong Joo Kim, Rea Lardelli, Balaji Sundararaman, John P Donohue, Ashkan Javaherian, Jens Lykke-Andersen, Steven Finkbeiner, C Frank Bennett, Manuel Ares, Christopher B Burge, J Paul Taylor, Frank Rigo, Gene W Yeo
HnRNPA2B1 encodes an RNA binding protein associated with neurodegeneration. However, its function in the nervous system is unclear. Transcriptome-wide crosslinking and immunoprecipitation in mouse spinal cord discover UAGG motifs enriched within ∼2,500 hnRNP A2/B1 binding sites and an unexpected role for hnRNP A2/B1 in alternative polyadenylation. HnRNP A2/B1 loss results in alternative splicing (AS), including skipping of an exon in amyotrophic lateral sclerosis (ALS)-associated D-amino acid oxidase (DAO) that reduces D-serine metabolism...
November 23, 2016: Neuron
Hong Wei, Hai-Yun Wu, Zuyue Chen, Ai-Niu Ma, Xiao-Fang Mao, Teng-Fei Li, Xin-Yan Li, Yong-Xiang Wang, Antti Pertovaara
Spinal transient receptor potential ankyrin 1 (TRPA1) channel is associated with various pain hypersensitivity conditions. Spinally, TRPA1 is expressed by central terminals of nociceptive nerve fibers and astrocytes. Among potential endogenous agonists of TRPA1 is H2O2 generated by d-amino acid oxidase (DAAO) in astrocytes. Here we studied whether prolonged block of the spinal TRPA1 or astrocytes starting at time of injury attenuates development and/or maintenance of neuropathic hypersensitivity. Additionally, TRPA1 and DAAO mRNA were determined in the dorsal root ganglion (DRG) and spinal dorsal horn (SDH)...
November 2016: Pharmacology, Biochemistry, and Behavior
Jumpei Sasabe, Yurika Miyoshi, Seth Rakoff-Nahoum, Ting Zhang, Masashi Mita, Brigid M Davis, Kenji Hamase, Matthew K Waldor
L-Amino acids are the building blocks for proteins synthesized in ribosomes in all kingdoms of life, but d-amino acids (d-aa) have important non-ribosome-based functions(1). Mammals synthesize d-Ser and d-Asp, primarily in the central nervous system, where d-Ser is critical for neurotransmission(2). Bacteria synthesize a largely distinct set of d-aa, which become integral components of the cell wall and are also released as free d-aa(3,4). However, the impact of free microbial d-aa on host physiology at the host-microbial interface has not been explored...
July 25, 2016: Nature Microbiology
Rochelle Ford, Susan J Quinn, Robert D O'Neill
Amperometric l-glutamate (Glu) biosensors, based on both wild-type and a recombinant form of l-glutamate oxidase (GluOx), were designed and characterized in terms of enzyme-kinetic, sensitivity and stability parameters in attempts to fabricate a real-time Glu monitoring device suitable for future long-term detection of this amino acid in biological and other complex media. A comparison of the enzyme from these two sources showed that they were similar in terms of biosensor performance. Optimization of the loading of the polycationic stabilization agent, polyethyleneimine (PEI), was established before investigating a range of crosslinking agents under different conditions: glutaraldehyde (GA), polyethylene glycol (PEG), and polyethylene glycol diglycidyl ether (PEGDE)...
2016: Sensors
Shogo Nakano, Kazuyuki Yasukawa, Takaki Tokiwa, Takeshi Ishikawa, Erika Ishitsubo, Naoya Matsuo, Sohei Ito, Hiroaki Tokiwa, Yasuhisa Asano
Elucidation of the molecular mechanism of amine oxidases (AOx) will help to extend their reactivity by rational design and their application to deracemization of various amine compounds. To date, several studies have been performed on S-selective AOx, but relatively few have focused on R-selective AOx. In this study, we sought to elucidate the mechanism of pkAOx, an R-selective AOx that we designed by introducing the Y228L and R283G mutations into d-amino acid oxidase from pig kidney. Four crystal structures of the substrate-bound protein and first-principles calculations based on the correlated fragment molecular orbital (FMO) indicated that two aromatic residues, Tyr224 and Phe242, form stable π-π stacking interaction with substrates...
October 10, 2016: Journal of Physical Chemistry. B
Chang-Liang Hou, Jing-Bo Wang, Hua Wu, Jia-Yu Liu, Zhi-Qing Ma, Jun-Tao Feng, Xing Zhang
Cytochrome c oxidase subunit II (COX II) containing a dual core CuA active site is one of the core subunits of mitochondrial Cytochrome c oxidase (Cco), which plays a significant role in the physiological process. In this report, the full-length cDNA of COXII gene was cloned from Sitophilus zeamais, which had an open reading frame (ORF) of 684 bp encoding 227 amino acids residues. The predicted COXII protein had a molecular mass of 26.2 kDa with pI value of 6.37. multiple sequence alignment and phylogenetic analysis indicated that Sitophilus zeamais COXII had high sequence identity with the COXII of other insect species...
September 30, 2016: Biochemical and Biophysical Research Communications
Kamil Karolczak, Anna Pieniazek, Cezary Watala
Homocysteine (Hcy) is an excitotoxic amino acid. It is potentially possible to prevent Hcy-induced toxicity, including haemostatic impairments, by antagonizing glutaminergic receptors. Using impedance aggregometry with arachidonate and collagen as platelet agonists, we tested whether the blockade of platelet NMDA (N-methyl-D-aspartate), AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) and kainate receptors with their inhibitors: MK-801 (dizocilpine hydrogen maleate, [5R,10S]-[+]-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine), CNQX (7-nitro-2,3-dioxo-1,4-dihydroquinoxaline-6-carbonitrile) and UBP-302 (2-{[3-[(2S)-2-amino-2-carboxyethyl]-2,6-dioxo-3,6-dihydropyrimidin 1(2H)-yl]methyl}benzoic acid) may hamper Hcy-dependent platelet aggregation...
January 2017: Platelets
Paulina Brodek, Beata Olas
Hydrogen sulfide (H2S) is a signaling gasotransmitter, involved in different physiological and pathological processes. H2S regulates apoptosis, the cell cycle and oxidative stress. H2S exerts powerful effects on smooth muscle cells, endothelial cells, inflammatory cells, endoplasmic reticulum, mitochondria and nuclear transcription factors. H2S is known to be produced from L-cysteine, D-cysteine and L-homocysteine in the body. Four enzymes - cystathionine-b synthase (CBS), mercaptopyruvate sulfurtransferase (3-MST), cystathionine-γ lyase (CSE) and cysteine aminotransferase (CAT) - are involved in H2S synthesis...
2016: Postȩpy Higieny i Medycyny Doświadczalnej
Reiko Koga, Yurika Miyoshi, Yu Sato, Masashi Mita, Ryuichi Konno, Wolfgang Lindner, Kenji Hamase
Two-dimensional high-performance liquid chromatographic (2D-HPLC) and 2D-HPLC-mass spectrometric (2D-HPLC-MS) systems have been designed and developed for the determination of the citrulline (Cit) and ornithine (Orn) enantiomers. Several d-amino acids have already been identified as novel physiologically active molecules and biomarkers, and the enantioselective evaluation of the amounts, distributions and metabolisms of non-proteinogenic amino acids gain as well increasing interest. In the present study, highly selective analytical methods were developed using a capillary monolithic ODS column (0...
October 7, 2016: Journal of Chromatography. A
Yingchen Ju, Shuilong Tong, Yongxiang Gao, Wei Zhao, Qi Liu, Qiong Gu, Jun Xu, Liwen Niu, Maikun Teng, Huihao Zhou
l-amino acid oxidases/deaminases (LAAOs/LAADs) are a class of oxidoreductases catalyzing the oxidative deamination of l-amino acids to α-keto acids. They are widely distributed in eukaryotic and prokaryotic organisms, and exhibit diverse substrate specificity, post-translational modifications and cellular localization. While LAAOs isolated from snake venom have been extensively characterized, the structures and functions of LAAOs from other species are largely unknown. Here, we reported crystal structure of a bacterial membrane-bound LAAD from Proteus vulgaris (pvLAAD) in complex with flavin adenine dinucleotide (FAD)...
September 2016: Journal of Structural Biology
Sandesh Panthi, Hyung-Joo Chung, Junyang Jung, Na Young Jeong
Hydrogen sulfide (H2S) is an emerging neuromodulator that is considered to be a gasotransmitter similar to nitrogen oxide (NO) and carbon monoxide (CO). H2S exerts universal cytoprotective effects and acts as a defense mechanism in organisms ranging from bacteria to mammals. It is produced by the enzymes cystathionine β-synthase (CBS), cystathionine ϒ-lyase (CSE), 3-mercaptopyruvate sulfurtransferase (MST), and D-amino acid oxidase (DAO), which are also involved in tissue-specific biochemical pathways for H2S production in the human body...
2016: Oxidative Medicine and Cellular Longevity
Esra Soydaş Akyol, Yakup Albayrak, Nurkan Aksoy, Başak Şahin, Murat Beyazyüz, Murat Kuloğlu, Kenji Hashimoto
OBJECTIVE: The product of the G72 gene is an activator of d-amino acid oxidase and has been suggested to play a role in the pathogenesis of schizophrenia. Increased G72 protein levels may be associated with disturbed glutamatergic transmission and increased reactive oxygen species. Only one pilot study by Lin et al. has investigated the potential role of serum G72 protein levels as a biomarker for schizophrenia. In this study, we aimed to compare serum G72 protein levels between patients with schizophrenia and healthy controls, and to retest the results of the previous pilot study...
July 14, 2016: Acta Neuropsychiatrica
Ariel J Santiago, Marwa N A Ahmed, Shu-Lin Wang, Krishna Damera, Binghe Wang, Phang C Tai, Eric S Gilbert, Charles D Derby
Escapin is an l-amino acid oxidase that acts on lysine to produce hydrogen peroxide (H2O2), ammonia, and equilibrium mixtures of several organic acids collectively called escapin intermediate products (EIP). Previous work showed that the combination of synthetic EIP and H2O2 functions synergistically as an antimicrobial toward diverse planktonic bacteria. We initiated the present study to investigate how the combination of EIP and H2O2 affected bacterial biofilms, using Pseudomonas aeruginosa as a model. Specifically, we examined concentrations of EIP and H2O2 that inhibited biofilm formation or fostered disruption of established biofilms...
September 2016: Antimicrobial Agents and Chemotherapy
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