5.1.1.18: serine racemase
This is an abbreviated version!
For detailed information about serine racemase, go to the full flat file.
Word Map on EC 5.1.1.18
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5.1.1.18
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d-serine
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n-methyl-d-aspartate
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co-agonist
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nmdars
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astrocyte
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d-amino
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schizophrenia
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neurotransmission
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pyridoxal
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hypofunction
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d-aspartate
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glutamatergic
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5'-phosphate-dependent
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nmda-type
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d-ser
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plp-dependent
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nmdar-mediated
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pharmacology
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medicine
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alanine-serine-cysteine
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drug development
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glycine-binding
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n-methyl-d
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vante
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brain-enriched
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gliotransmitter
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nmdar-dependent
- 5.1.1.18
- d-serine
- n-methyl-d-aspartate
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co-agonist
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nmdars
- astrocyte
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d-amino
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schizophrenia
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neurotransmission
- pyridoxal
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hypofunction
- d-aspartate
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glutamatergic
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5'-phosphate-dependent
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nmda-type
- d-ser
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plp-dependent
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nmdar-mediated
- pharmacology
- medicine
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alanine-serine-cysteine
- drug development
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glycine-binding
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n-methyl-d
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vante
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brain-enriched
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gliotransmitter
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nmdar-dependent
Reaction
Synonyms
hSR, More, RiSR, RLO149_c015450, Ser racemase, SerR, SRace, SRR, T01H8.2, Zm-SR, ZmSR
ECTree
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General Information
General Information on EC 5.1.1.18 - serine racemase
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evolution
malfunction
physiological function
additional information
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the eukaryotic serine racemase from Dictyostelium discoideum is a fold-type II pyridoxal 5'-phosphate-dependent enzyme
evolution
SerRs and AspRs are not separated by their racemase functions and form a serine/aspartate racemase family cluster based on phylogenetic analysis
evolution
SerRs and AspRs are not separated by their racemase functions and form a serine/aspartate racemase family cluster based on phylogenetic analysis, the organism has two paralogous genes, SerR and AspR. The presence of the triple serine loop region in both AspRs and SerRs leads to greater AspR activity while removing the triple serine loop region results in almost complete loss of AspR activity
evolution
SerRs and AspRs are not separated by their racemase functions and form a serine/aspartate racemase family cluster based on phylogenetic analysis, the organism has two paralogous genes, SerR and AspR. The presence of the triple serine loop region in both AspRs and SerRs leads to greater AspR activity while removing the triple serine loop region results in almost complete loss of AspR activity
evolution
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SerRs and AspRs are not separated by their racemase functions and form a serine/aspartate racemase family cluster based on phylogenetic analysis, the organism has two paralogous genes, SerR and AspR. The presence of the triple serine loop region in both AspRs and SerRs leads to greater AspR activity while removing the triple serine loop region results in almost complete loss of AspR activity
evolution
the enzyme belongs to the fold-type II group of pyridoxal 5'-phosphate enzymes
evolution
the enzyme from Zea mays belongs to the type II PLP-dependent enzymes and differs from the enzyme of a vancomycin-resistant bacterium
evolution
Roseobacter litoralis ATCC 49566 / DSM 6996 / JCM 21268 / NBRC 15278 / OCh 149
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the enzyme belongs to the fold-type II group of pyridoxal 5'-phosphate enzymes
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increased levels of enzyme-mediated D-serine production are associated with amyotrophic lateral sclerosis and Alzheimer's disease
malfunction
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serine racemase is associated with schizophrenia susceptibility in a mouse model, abnormal N-methyl-D-aspartate receptor function is implicated in the pathophysiology of schizophrenia
malfunction
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serine racemase is associated with schizophrenia susceptibility in humans, abnormal N-methyl-D-aspartate receptor function is implicated in the pathophysiology of schizophrenia
malfunction
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enzyme knockout mice show increased expression of involucrin and keratin 10 in the epidermis compared to wild-type mice
malfunction
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enzyme KO mutant mice show reduced D-serine contents, reduced N-methyl-D-aspartate receptor activity, and impaired learning and memory abilities, altered morphological features of brain of SR-KO mice, altered behaviur and neurodegeneration in KO mice, phenotypes of three SR-KO mouse strains, overview. Enzyme expression in the liver is upregulated in nSR-KO_ITC mice
malfunction
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mice genetically deficient in the serine racemase gene have decreased levels of D-serine in the brain. Serine racemase KO mice show no obvious defects, but neurotransmission and behavior mediated by the NMDA receptors are altered in these mice. The KO mice exhibit a schizophrenia-like phenotype and have impaired spatial memory, reduced prepulse inhibition, decreased sociability, and elevated anxiety. KO mice have a decreased level of D-serine, which protected against overstimulation of NMDA receptors
malfunction
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repeated administration of methamphetamine results in behavioral sensitization in wild-type, but not in knockout mutant Srr-KO mice, while METH-induced acute hyperlocomotion is similar in wild-type and mutant mice. Pretreatment with D-serine does not affect the development of behavioral sensitization after repeated methamphetamine administration
malfunction
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serine racemase is implicated with NMDA receptor dysfunction and schizophrenia
malfunction
D-Asp levels are significantly lower in the hippocampi and frontal cortices of SRR-knockout mice, approximately half the levels recorded from wild-type mice. These results are consistent with those from a previous study. In contrast, D-Asp abundance is not altered in the cerebellums or testes of SRR-knockout mice
malfunction
HEK-293T cells expressing the wild-type enzyme and hyperactive mutant Q155D show resistance to staurosporine-induced apoptosis, compared with nontransfected HEK-293T cells and cells expressing the catalytically-dead enzyme mutant K56G. The wild-type enzyme-expressing cells also show a significant higher viability than the cells expressing hyperactive mutant Q155D enzyme mutant. Elevated phosphorylation levels of Bcl-2 at Ser70 and Akt at Ser473 and Thr308, which are related to cell survival, occur in the cells expressing wild-type enzyme and mutant Q155D, elevated levels of acetyl CoA and ATP in cells expressing the wild-type enzyme. Phenotypes, overview
malfunction
no significant decreases in the intracellular D-Asp levels are observed in the SRR-KO cells, the intracellular concentration of D-Ser in the SRR-KO PC12 cells is visibly lower than that in the controls
malfunction
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serine racemase is associated with schizophrenia susceptibility in a mouse model, abnormal N-methyl-D-aspartate receptor function is implicated in the pathophysiology of schizophrenia
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malfunction
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enzyme KO mutant mice show reduced D-serine contents, reduced N-methyl-D-aspartate receptor activity, and impaired learning and memory abilities, altered morphological features of brain of SR-KO mice, altered behaviur and neurodegeneration in KO mice, phenotypes of three SR-KO mouse strains, overview. Enzyme expression in the liver is upregulated in nSR-KO_ITC mice
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malfunction
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enzyme knockout mice show increased expression of involucrin and keratin 10 in the epidermis compared to wild-type mice
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inhibition of D-serine synthesis caused by translocation of the enzyme to the membrane provides a fail-safe mechanism to prevent NMDA receptor overactivation in vicinal cells or synapses
physiological function
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the enzyme is responsible for D-serine production in the central nervous system, where D-serine acts as a co-agonist of the N-methyl-D-aspartate receptor ion channels
physiological function
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the enzyme is responsible for the biosynthesis of the neurotransmitter D-serine, which activates N-methyl-D-aspartate receptors in the central nervous system
physiological function
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serine racemase catalyses the synthesis of the transmitter/neuromodulator D-serine, which plays a major role in synaptic plasticity and N-methyl D-aspartate receptor neurotoxicity
physiological function
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D-serine is an endogenous coagonist of the N-methyl-D-aspartate-type glutamate receptor in the central nervous system and its synthesis is catalyzed by serine racemase
physiological function
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D-serine, synthesized by the enzyme, is an important coagonist at the NR1 subunit of the NMDA receptor class of glutamate receptors
physiological function
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role of D-serine as an endogenous agonist of N-methyl-D-aspartate receptors (NMDARs). D-Serine is required for NMDAR activity during normal neurotransmission as well as NMDAR overactivation that takes place in neurodegenerative conditions
physiological function
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serine racemase activity is regulated by several physiological pathways. D-Serine binds to the coagonist site of the NMDA receptors and enhances neurotransmission
physiological function
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serine racemase activity is regulated by several physiological pathways. D-Serine binds to the coagonist site of the NMDA receptors and enhances neurotransmission
physiological function
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serine racemase activity is regulated by several physiological pathways. D-Serine binds to the coagonist site of the NMDA receptors and enhances neurotransmission
physiological function
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serine racemase is a key player in neuron activity and in neuropathologies. D-serine is the essential co-agonist of the N-methyl-D-aspartate receptor, that mediates neurotransmission, synaptic plasticity, cell migration and long term potentiation. High and low D-serine levels have been associated with distinct neuropathologies, aging-related deficits and psychiatric disorders due to either hyper- or hypo-activation of the receptor. Serine racemase dual activity is regulated by ATP, divalent cations, cysteine nitrosylation, post-translational modifications, and interactions with proteins that bind either at the N- or C-terminus. Molecular basis of catalysis, regulation and conformational plasticity, overview
physiological function
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serine racemase is an enzyme which synthesizes D-serine, an endogenous co-agonist of N-methyl-D-aspartate (NMDA) receptors. N-methyl-D-aspartate receptors play a role in behavioral abnormalities observed after administration of the psychostimulant, methamphetamine. Role of serine racemase in behavioral sensitization in mice after repeated administration of methamphetamine, overview
physiological function
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through cross-talk between allosteric and active sites, intracellular ATP and glycine control D-serine homeostasis, and, indirectly, NMDA receptor activity. The N-methyl D-aspartate (NMDA) receptors play a key role in excitatory neurotransmission, and control learning, memory and synaptic plasticity. Their activity is modulated by the agonist glutamate and by the co-agonists D-serine and glycine
physiological function
free D-serine (D-Ser) plays a crucial role in regulating brain function in mammals. In the brain, D-Ser is synthesized by Ser racemase, the enzyme produces D-Ser from L-Ser in a pyridoxal 5'-phosphate-dependent manner. D-Ser binds to the glycine-binding site of the NMDA receptor and potentiates glutamatergic neurotransmission in the central nervous system. Astroglia and/or neuron-derived D-Ser regulates NMDA receptor-dependent long-term potentiation and/or depression in hypothalamic and hippocampal excitatory synapses. Ser racemase also exhibits dehydratase activity toward several hydroxyamino acids
physiological function
human serine racemase catalyzes both the synthesis and the degradation of D-serine, an obligatory co-agonist of the glutamatergic NMDA receptors. It is allosterically controlled by ATP, which increases its activity around 7fold through a cooperative binding mechanism. Serine racemase is allosterically inhibited by NADH and reduced nicotinamide derivatives suggesting a physiological regulation of hSR activity by the glycolytic flux in neurons. NADH binding counteracts ATP activation of the enzyme with a complete loss of cooperativity
physiological function
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many endospore-forming bacteria embed alanine racemases into their spore coats, and these enzymes are thought to convert the L-alanine germinant into D-alanine, a spore germination inhibitor. Clostridium difficile spores can respond to a diverse set of amino acid co-germinants and alanine racemase 2, Alr2, EC 5.1.1.1, can accommodate serine as a substrate. L-alanine is a co-germinant, and D-alanine also functions as a co-germinant. L- and D-serine are also co-germinants for Clostridium difficile spores. Only the L-form of alanine can trigger spore germination when added with taurocholic acid. Gene alr2 is dispensable for germination in response to L-alanine but essential for germination in response to D-alanine
physiological function
most of the endogenous free D-serine (about 90%) in the brain is produced by serine racemase. D-Serine in the brain is involved in neurodegenerative disorders and epileptic states as an endogenous co-agonist of the NMDA-type glutamate receptor
physiological function
rat PC-12 cells rely on a non-SRR-based mechanism to produce the majority of its D-Asp
physiological function
serine racemase (SerR) is a pyridoxal 5'-phosphate-dependent enzyme catalyzing the racemization of L-Ser to D-Ser. In mammals, D-Ser is an endogenous coagonist required for the activation of N-methyl-D-aspartate receptors (NMDARs)
physiological function
serine racemase (SerR) is a pyridoxal 5'-phosphate-dependent enzyme catalyzing the racemization of L-Ser to D-Ser. In mammals, D-Ser is an endogenous coagonist required for the activation of N-methyl-D-aspartate receptors (NMDARs)
physiological function
serine racemase catalyzes the production of D-serine, a co-agonist of the N-methyl-D-aspartatereceptor (NMDAR), contribution of the enzyme in the NMDAR-mediated neuronal cell death process. The racemization reaction catalyzed by serine racemase may have a more protective role against apoptosis than the alpha,beta-elimination reaction
physiological function
serine racemase is a key player in apoptosis and necrosis
physiological function
serine racemase is a key player in apoptosis and necrosis, physiological regulation of serine racemase, overview. NMDAR-mediated Ca2+ influx at postsynaptic neurons involves Ca2+/calmodulin-dependent activation of neuronal NO synthase. The NO produced here diffuses into adjacent astrocytes or neurons to nitrosylate and inhibit the serine racemase and activate D-amino acid oxidase (DAAO). Cys113, identified as the target residue of serine racemase nitrosylation, is in close proximity to the ATP-binding region and thus nitrosylation might displace ATP from its binding site and inactivate the enzyme. ATP and NO reciprocally activate and inhibit the enzyme by acting at the same protein site. Synthesis of both neuronal and astrocytic D-serine in the brain is dependent on 3-phosphoglycerate dehydrogenase, an enzyme that occurs mainly in astrocytes and which catalyzes the first step in L-serine biosynthesis: L-serine shuttles from astrocytes into neurons where it is transformed by neuronal SR to D-serine. Serine racemase D-serine-related pathway in neuronal apoptosis, D-serine and the enzyme are involved in controlling the extent of NMDAR activation and neurotoxic insults observed in many central nervous disorders, like Alzheimer's disease, amylothrophic lateral sclerosis (ALS), and epilepsy, and also stroke and ischemia, detailed overview
physiological function
serine racemase is a pyridoxal 5'-phosphate dependent enzyme responsible for the synthesis of D-serine, a neuromodulator of the NMDA receptors. Its activity is modulated by several ligands, including ATP, divalent cations and protein interactors. The enzyme is negatively regulated by reversible S-nitrosylation of cysteine residues, C113, C128, and C269, overview
physiological function
serine racemase, SRR, is involved in D-aspartate biosynthesis, SRR is responsible for D-Asp production in certain organs and/or tissues
physiological function
the enzyme is responsible for D-serine biosynthesis in vivo
physiological function
the mammalian Ser racemase homologue encoded by T01H8.2 from Caenorhabditis elegans exhibits racemase activity, it also shows dehydratase activity toward several hydroxyamino acids. The enzyme is not critical for Ser metabolism in vico. T01H8.2 Ser, Asp, and Ala racemase activities are one to two orders of magnitude lower than those of human Ser racemase. Other than the T01H8.2 gene, there is no known gene within the Caenorhabditis elegans genome that is orthologous to a Ser racemase gene, therefore, D-Ser may be biosynthesized by an enzyme(s) that does not belong to the Ser racemase family, or an enzyme that has not yet been classified as a member of this family.T01H8.2 exhibit higher dehydratase activity toward L-THA in vitro, T01H8.2 might play a role in the metabolism of this amino acid in vivo. T01H8.2-mediated dehydration of diet-derived L-THA may be necessary to avoid toxicity
physiological function
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many endospore-forming bacteria embed alanine racemases into their spore coats, and these enzymes are thought to convert the L-alanine germinant into D-alanine, a spore germination inhibitor. Clostridium difficile spores can respond to a diverse set of amino acid co-germinants and alanine racemase 2, Alr2, EC 5.1.1.1, can accommodate serine as a substrate. L-alanine is a co-germinant, and D-alanine also functions as a co-germinant. L- and D-serine are also co-germinants for Clostridium difficile spores. Only the L-form of alanine can trigger spore germination when added with taurocholic acid. Gene alr2 is dispensable for germination in response to L-alanine but essential for germination in response to D-alanine
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physiological function
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role of D-serine as an endogenous agonist of N-methyl-D-aspartate receptors (NMDARs). D-Serine is required for NMDAR activity during normal neurotransmission as well as NMDAR overactivation that takes place in neurodegenerative conditions
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physiological function
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D-serine is an endogenous coagonist of the N-methyl-D-aspartate-type glutamate receptor in the central nervous system and its synthesis is catalyzed by serine racemase
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physiological function
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the mammalian Ser racemase homologue encoded by T01H8.2 from Caenorhabditis elegans exhibits racemase activity, it also shows dehydratase activity toward several hydroxyamino acids. The enzyme is not critical for Ser metabolism in vico. T01H8.2 Ser, Asp, and Ala racemase activities are one to two orders of magnitude lower than those of human Ser racemase. Other than the T01H8.2 gene, there is no known gene within the Caenorhabditis elegans genome that is orthologous to a Ser racemase gene, therefore, D-Ser may be biosynthesized by an enzyme(s) that does not belong to the Ser racemase family, or an enzyme that has not yet been classified as a member of this family.T01H8.2 exhibit higher dehydratase activity toward L-THA in vitro, T01H8.2 might play a role in the metabolism of this amino acid in vivo. T01H8.2-mediated dehydration of diet-derived L-THA may be necessary to avoid toxicity
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a A65S hSDH mutant of serine dehydratase, EC 4.2.1.13, acquires an additional function of using D-serine as a substrate
additional information
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a A65S hSDH mutant of serine dehydratase, EC 4.2.1.13, acquires an additional function of using D-serine as a substrate
additional information
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circular dichroism spectral analysis of wild-type and mutant enzymes, overview
additional information
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rat serine racemase lacks the C-terminal PDZrecognition sequence
additional information
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roles of quaternary structure and cysteine residues in the activity of human serine racemase, structure-function relationships of the recombinant enzyme, overview
additional information
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Alr2 racemase is the sixth most highly expressed gene during Clostridium difficile spore formation
additional information
enzyme activity site structure, docking and modeling, overview
additional information
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enzyme activity site structure, docking and modeling, overview
additional information
enzyme activity site structure, docking and modeling, overview
additional information
homology modeling of the ligand-free form of the human enzyme, in which the X-ray crystal structure of ligand-free rat enzyme, PDB ID 3HMK, is used as a template
additional information
role of individual residues at position 150-152, overview
additional information
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role of individual residues at position 150-152, overview
additional information
role of individual residues at position 150-152, overview
additional information
role of individual residues at position 150-152, overview
additional information
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role of individual residues at position 150-152, overview
additional information
structural comparison with Rattus norvegicus and Schizosaccharomyces pombe serine racemases reveals a similar arrangement of active-site residues but a different orientation of the C-terminal helix, structure modeling, overview. Active site structure comparisons
additional information
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structural comparison with Rattus norvegicus and Schizosaccharomyces pombe serine racemases reveals a similar arrangement of active-site residues but a different orientation of the C-terminal helix, structure modeling, overview. Active site structure comparisons
additional information
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Alr2 racemase is the sixth most highly expressed gene during Clostridium difficile spore formation
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