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Serine racemase

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https://www.readbyqxmd.com/read/29124361/involvement-of-c-terminal-amino-acids-of-a-hyperthermophilic-serine-racemase-in-its-thermostability
#1
Masahito Murakami, Makoto Saito, Hirokazu Yokobori, Katsushi Nishimura, Minoru Tanigawa, Yoko Nagata
Pyrobaculum islandicum is a hyperthermophilic archaeon that grows optimally at 95-100 °C. In the previous study, we extensively purified a serine racemase from this organism and cloned the gene for overexpression in Escherichia coli (Ohnishi et al. 2008). This enzyme also exhibits highly thermostable L-serine/L-threonine dehydratase activity. In the present study, we aimed to elucidate the molecular mechanisms underlying the high thermostability of this enzyme. A recombinant variant of this enzyme, PiSRvt, constructed by truncating the C-terminal 72 amino acids, was compared with the native enzyme, PiSR...
November 9, 2017: Extremophiles: Life Under Extreme Conditions
https://www.readbyqxmd.com/read/29025687/serine-racemase-and-d-serine-in-the-amygdala-are-dynamically-involved-in-fear-learning
#2
Darrick T Balu, Kendall Taylor Presti, Cathy C Y Huang, Kevin Muszynski, Inna Radzishevsky, Herman Wolosker, Guia Guffanti, Kerry J Ressler, Joseph T Coyle
BACKGROUND: The amygdala is a central component of the neural circuitry that underlies fear learning. N-methyl-D-aspartate receptor-dependent plasticity in the amygdala is required for pavlovian fear conditioning and extinction. N-methyl-D-aspartate receptor activation requires the binding of a coagonist, D-serine, which is synthesized from L-serine by the neuronal enzyme serine racemase (SR). However, little is known about SR and D-serine function in the amygdala. METHODS: We used immunohistochemical methods to characterize the cellular localization of SR and D-serine in the mouse and human amygdala...
August 26, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/28966065/involvement-of-neuronal-and-glial-activities-in-control-of-the-extracellular-d-serine-concentrations-by-the-ampa-glutamate-receptor-in-the-mouse-medial-prefrontal-cortex
#3
Sayuri Ishiwata, Asami Umino, Toru Nishikawa
It has been well accepted that d-serine may be an exclusive endogenous coagonist for the N-methyl-d-aspartate (NMDA)-type glutamate receptor in mammalian forebrain regions. We have recently found by using an in vivo dialysis method that an intra-medial prefrontal cortex infusion of S-α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (S-AMPA), a selective AMPA-type glutamate receptor agonist, causes a reduction in the extracellular levels of d-serine in a calcium-permeable AMPA receptor antagonist-sensitive manner...
September 28, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28939329/potential-deficit-from-decreased-cerebellar-granule-cell-migration-in-serine-racemase-deficient-mice-is-reversed-by-increased-expression-of-glun2b-and-elevated-levels-of-nmdar-agonists
#4
He Zhang, Liping Song, Yuhua Chang, Mengjuan Wu, Xiuli Kuang, Haiyan Jiang, Shengzhou Wu
Inward migration of cerebellar granule cells (CGCs) after birth is critical for lamination in the cerebellar cortex. N-methyl-d-aspartate (NMDA) subtype of glutamate receptor (NMDAR) tethering CGCs into Bergmann glial fibers mediates the inward movement during the glial-dependent migratory phase. Activation of NMDAR depends on simultaneous binding of the GluN2 subunit by glutamate, and of the GluN1 subunit by d-serine or glycine; d-serine is believed to be an endogenous ligand of NMDAR. We hypothesized that lamination of the cerebellar cortex may be compromised in Srr (the gene for serine racemase (SR)) mutated mice (Srrnull) because of significantly low levels of d-serine per se...
September 20, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28892569/serine-racemase-deficiency-attenuates-choroidal-neovascularization-and-reduces-nitric-oxide-and-vegf-levels-by-retinal-pigment-epithelial-cells
#5
Haiyan Jiang, Mengjuan Wu, Yimei Liu, Liping Song, Shifeng Li, Xianwei Wang, Yun-Feng Zhang, Junxu Fang, Shengzhou Wu
Choroidal neovascularization (CNV) is a leading cause of blindness in age-related macular degeneration. Production of vascular endothelial growth factor (VEGF) and macrophage recruitment by retinal pigment epithelial cells (RPE) significantly contributes to the process of CNV in an experimental CNV model. Serine racemase (SR) is expressed in retinal neurons and glial cells, and its product, d-serine, is an endogenous co-agonist of N-methyl-d-aspartate receptor. Activation of the receptor results in production of nitric oxide ((...
November 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28836020/change-of-the-n-terminal-codon-bias-combined-with-trna-supplementation-outperforms-the-selected-fusion-tags-for-production-of-human-d-amino-acid-oxidase-as-active-inclusion-bodies
#6
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...
November 2017: Biotechnology Letters
https://www.readbyqxmd.com/read/28714867/enhanced-astrocytic-d-serine-underlies-synaptic-damage-after-traumatic-brain-injury
#7
Enmanuel J Perez, Stephen A Tapanes, Zachary B Loris, Darrick T Balu, Thomas J Sick, Joseph T Coyle, Daniel J Liebl
After traumatic brain injury (TBI), glial cells have both beneficial and deleterious roles in injury progression and recovery. However, few studies have examined the influence of reactive astrocytes in the tripartite synapse following TBI. Here, we have demonstrated that hippocampal synaptic damage caused by controlled cortical impact (CCI) injury in mice results in a switch from neuronal to astrocytic d-serine release. Under nonpathological conditions, d-serine functions as a neurotransmitter and coagonist for NMDA receptors and is involved in mediating synaptic plasticity...
August 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28696262/human-serine-racemase-structure-activity-relationship-studies-provide-mechanistic-insight-and-point-to-position-84-as-a-hot-spot-for-%C3%AE-elimination-function
#8
COMPARATIVE STUDY
David L Nelson, Greg A Applegate, Matthew L Beio, Danielle L Graham, David B Berkowitz
There is currently great interest in human serine racemase, the enzyme responsible for producing the NMDA co-agonist d-serine. Reported correlation of d-serine levels with disorders including Alzheimer's disease, ALS, and ischemic brain damage (elevated d-serine) and schizophrenia (reduced d-serine) has further piqued this interest. Reported here is a structure/activity relationship study of position Ser(84), the putative re-face base. In the most extreme case of functional reprogramming, the S84D mutant displays a dramatic reversal of β-elimination substrate specificity in favor of l-serine over the normally preferred l-serine-O-sulfate (∼1200-fold change in kcat/Km ratios) and l (l-THA; ∼5000-fold change in kcat/Km ratios) alternative substrates...
August 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28681245/an-overview-on-d-amino-acids
#9
REVIEW
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
https://www.readbyqxmd.com/read/28674984/schizophrenia-basic-and-clinical
#10
Joseph T Coyle
Schizophrenia is a chronic severe mental disorder characterized by psychosis, cognitive impairments, and social and motivational deficits. It is associated with a progressive loss of cortical volume after onset of psychosis; nevertheless, cortical atrophy correlates with the cognitive impairments and the negative symptoms but not with the psychosis. The cortical atrophy is not primarily due to neuronal degeneration but rather to neuronal atrophy and loss of glutamatergic synapses. A downregulation of the presynaptic markers for the parvalbumin-expressing GABAergic interneurons that provide recurrent inhibition to cortical pyramidal neurons is another consistent pathologic feature...
2017: Advances in Neurobiology
https://www.readbyqxmd.com/read/28560262/decreased-free-d-aspartate-levels-are-linked-to-enhanced-d-aspartate-oxidase-activity-in-the-dorsolateral-prefrontal-cortex-of-schizophrenia-patients
#11
Tommaso Nuzzo, Silvia Sacchi, Francesco Errico, Simona Keller, Orazio Palumbo, Ermanno Florio, Daniela Punzo, Francesco Napolitano, Massimiliano Copetti, Massimo Carella, Lorenzo Chiariotti, Alessandro Bertolino, Loredano Pollegioni, Alessandro Usiello
It is long acknowledged that the N-methyl d-aspartate receptor co-agonist, d-serine, plays a crucial role in several N-methyl d-aspartate receptor-mediated physiological and pathological processes, including schizophrenia. Besides d-serine, another free d-amino acid, d-aspartate, is involved in the activation of N-methyl d-aspartate receptors acting as an agonist of this receptor subclass, and is abundantly detected in the developing human brain. Based on the hypothesis of N-methyl d-aspartate receptor hypofunction in the pathophysiology of schizophrenia and considering the ability of d-aspartate and d-serine to stimulate N-methyl d-aspartate receptor-dependent transmission, in the present work we assessed the concentration of these two d-amino acids in the post-mortem dorsolateral prefrontal cortex and hippocampus of patients with schizophrenia and healthy subjects...
2017: NPJ Schizophrenia
https://www.readbyqxmd.com/read/28533113/a-novel-serine-racemase-inhibitor-suppresses-neuronal-over-activation-in-vivo
#12
Hisashi Mori, Ryogo Wada, Satoyuki Takahara, Yoshikazu Horino, Hironori Izumi, Tetsuya Ishimoto, Tomoyuki Yoshida, Mineyuki Mizuguchi, Takayuki Obita, Hiroaki Gouda, Shuichi Hirono, Naoki Toyooka
Serine racemase (SRR) is an enzyme that produces d-serine from l-serine. d-Serine acts as an endogenous coagonist of NMDA-type glutamate receptors (NMDARs), which regulate many physiological functions. Over-activation of NMDARs induces excitotoxicity, which is observed in many neurodegenerative disorders and epilepsy states. In our previous works on the generation of SRR gene knockout (Srr-KO) mice and its protective effects against NMDA- and Aβ peptide-induced neurodegeneration, we hypothesized that the regulation of NMDARs' over-activation by inhibition of SRR activity is one such therapeutic strategy to combat these disease states...
July 15, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28487371/a-clostridium-difficile-alanine-racemase-affects-spore-germination-and-accommodates-serine-as-a-substrate
#13
Ritu Shrestha, Steve W Lockless, Joseph A Sorg
Clostridium difficile has become one of the most common bacterial pathogens in hospital-acquired infections in the United States. Although C. difficile is strictly anaerobic, it survives in aerobic environments and transmits between hosts via spores. C. difficile spore germination is triggered in response to certain bile acids and glycine. Although glycine is the most effective co-germinant, other amino acids can substitute with varying efficiencies. Of these, l-alanine is an effective co-germinant and is also a germinant for most bacterial spores...
June 23, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28435276/clinical-and-biochemical-study-of-d-serine-metabolism-among-schizophrenia-patients
#14
Hamdy N El-Tallawy, Tahia H Saleem, Abdallah Maa El-Ebidi, Mohammed H Hassan, Romany H Gabra, Wafaa Ma Farghaly, Nagwa Abo El-Maali, Hoda S Sherkawy
BACKGROUND: Schizophrenia is a typical N-methyl-d-aspartate receptor (NMDA-R) hypofunction disorder. Decreased d-serine (d-Ser) levels in the periphery occur in schizophrenia and may reflect decreased availability of d-Ser to activate NMDA-R in the brain. OBJECTIVE: The objective of this study was to investigate the role of d-Ser metabolism in the pathogenesis of schizophrenia via biochemical assays and correlates, the serum level of d-Ser, d-serine racemase (SR) (responsible for its formation from l-serine [l-Ser]) and d-amino acid oxidase (DAAO) (responsible for its catabolism), among different clinical types of schizophrenia patients...
2017: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/28290777/isolation-and-amino-acid-sequence-of-a-dehydratase-acting-on-d-erythro-3-hydroxyaspartate-from-pseudomonas-sp-n99-and-its-application-in-the-production-of-optically-active-3-hydroxyaspartate
#15
Hiroyuki Nagano, Kana Shibano, Yu Matsumoto, Atsushi Yokota, Masaru Wada
An enzyme catalyzing the ammonia-lyase reaction for the conversion of d-erythro-3-hydroxyaspartate to oxaloacetate was purified from the cell-free extract of a soil-isolated bacterium Pseudomonas sp. N99. The enzyme exhibited ammonia-lyase activity toward l-threo-3-hydroxyaspartate and d-erythro-3-hydroxyaspartate, but not toward other 3-hydroxyaspartate isomers. The deduced amino acid sequence of the enzyme, which belongs to the serine/threonine dehydratase family, shows similarity to the sequence of l-threo-3-hydroxyaspartate ammonia-lyase (EC 4...
June 2017: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/28202572/differential-regulation-of-nmda-receptors-by-d-serine-and-glycine-in-mammalian-spinal-locomotor-networks
#16
David Acton, Gareth B Miles
Activation of N-methyl-d-aspartate receptors (NMDARs) requires the binding of a coagonist, either d-serine or glycine, in addition to glutamate. Changes in occupancy of the coagonist binding site are proposed to modulate neural networks including those controlling swimming in frog tadpoles. Here, we characterize regulation of the NMDAR coagonist binding site in mammalian spinal locomotor networks. Blockade of NMDARs by d(-)-2-amino-5-phosphonopentanoic acid (d-APV) or 5,7-dichlorokynurenic acid reduced the frequency and amplitude of pharmacologically induced locomotor-related activity recorded from the ventral roots of spinal-cord preparations from neonatal mice...
May 1, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28089597/magnesium-and-calcium-ions-differentially-affect-human-serine-racemase-activity-and-modulate-its-quaternary-equilibrium-toward-a-tetrameric-form
#17
Stefano Bruno, Marilena Margiotta, Francesco Marchesani, Gianluca Paredi, Valentina Orlandi, Serena Faggiano, Luca Ronda, Barbara Campanini, Andrea Mozzarelli
Serine racemase is the pyridoxal 5'-phosphate dependent enzyme that catalyzes both production and catabolism of d-serine, a co-agonist of the NMDA glutamate receptors. Mg(2+), or, alternatively, Ca(2+), activate human serine racemase by binding both at a specific site and - as ATP-metal complexes - at a distinct ATP binding site. We show that Mg(2+) and Ca(2+) bind at the metal binding site with a 4.5-fold difference in affinity, producing a similar thermal stabilization and partially shifting the dimer-tetramer equilibrium in favour of the latter...
April 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28051338/activity-dependent-sulfhydration-signal-controls-n-methyl-d-aspartate-subtype-glutamate-receptor-dependent-synaptic-plasticity-via-increasing-d-serine-availability
#18
Yuan-Long Li, Peng-Fei Wu, Jian-Guo Chen, Sheng Wang, Qian-Qian Han, Dan Li, Wen Wang, Xin-Lei Guan, Di Li, Li-Hong Long, Jian-Geng Huang, Fang Wang
AIMS: Reactive sulfur species, including hydrogen sulfide (H2S) and its oxydates, have been raised as novel redox signaling molecules. The present study aimed at examining whether endogenous sulfhydration signal is required for long-term potentiation (LTP), a cellular model for memory. RESULTS: In this study, we found that increased synaptic activity triggered sulfide generation and protein sulfhydration. Activity-triggered sulfide production was essential for N-methyl-D-aspartate subtype glutamate receptor (NMDAR)-dependent LTP via maintaining the availability of d-serine, a primary coagonist for synaptic NMDARs...
September 1, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/27986591/spinal-d-serine-increases-pkc-dependent-glun1-phosphorylation-contributing-to-the-sigma-1-receptor-induced-development-of-mechanical-allodynia-in-a-mouse-model-of-neuropathic-pain
#19
Sheu-Ran Choi, Ji-Young Moon, Dae-Hyun Roh, Seo-Yeon Yoon, Soon-Gu Kwon, Hoon-Seong Choi, Suk-Yun Kang, Ho-Jae Han, Alvin J Beitz, Jang-Hern Lee
We have recently shown that spinal sigma-1 receptor (Sig-1R) activation facilitates nociception via an increase in phosphorylation of the N-methyl-D-aspartate (NMDA) receptor GluN1 subunit (pGluN1). The present study was designed to examine whether the Sig-1R-induced facilitative effect on NMDA-induced nociception is mediated by D-serine, and whether D-serine modulates spinal pGluN1 expression and the development of neuropathic pain after chronic constriction injury (CCI) of the sciatic nerve. Intrathecal administration of the D-serine degrading enzyme, D-amino acid oxidase attenuated the facilitation of NMDA-induced nociception induced by the Sig-1R agonist, 2-(4-morpholinethyl)1-phenylcyclohexane carboxylate...
April 2017: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/27880078/serine-racemase-is-expressed-in-islets-and-contributes-to-the-regulation-of-glucose-homeostasis
#20
Amber D Lockridge, Daniel C Baumann, Brian Akhaphong, Alleah Abrenica, Robert F Miller, Emilyn U Alejandro
NMDA receptors (NMDARs) have recently been discovered as functional regulators of pancreatic β-cell insulin secretion. While these excitatory receptor channels have been extensively studied in the brain for their role in synaptic plasticity and development, little is known about how they work in β-cells. In neuronal cells, NMDAR activation requires the simultaneous binding of glutamate and a rate-limiting co-agonist, such as D-serine. D-serine levels and availability in most of the brain rely on endogenous synthesis by the enzyme serine racemase (Srr)...
November 2016: Islets
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