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Information on EC 5.1.1.18 - serine racemase and Organism(s) Rattus norvegicus and UniProt Accession Q76EQ0

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     5 Isomerases
         5.1 Racemases and epimerases
             5.1.1 Acting on amino acids and derivatives
                5.1.1.18 serine racemase
IUBMB Comments
A pyridoxal-phosphate protein that is highly selective for L-serine as substrate. D-Serine is found in type-II astrocytes in mammalian brain, where it appears to be an endogenous ligand of the glycine site of N-methyl-D-aspartate (NMDA) receptors [1,2]. The reaction can also occur in the reverse direction but does so more slowly at physiological serine concentrations .
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This record set is specific for:
Rattus norvegicus
UNIPROT: Q76EQ0
Word Map
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
The taxonomic range for the selected organisms is: Rattus norvegicus
Reaction Schemes
Synonyms
hSR, More, RiSR, RLO149_c015450, Ser racemase, SerR, SRace, SRR, T01H8.2, Zm-SR, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SerR
283173
-
additional information
283173
cf. EC 5.1.1.13
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
L-serine = D-serine
show the reaction diagram
analysis of the catalytic reaction mechanism and intermediate stabilization in mammalian serine racemase using multiscale quantum-classical simulations, hybrid quantum mechanics/molecular mechanics molecular dynamics simulations in conjunction with umbrella sampling are performed, overview. The unprotonated pyridoxal 5'-phosphate-substrate intermediate is stabilized mostly due to solvation effects contributed by water molecules and active-site residues, as well as long-range electrostatic interactions with the enzyme environment
-
L-serine = D-serine
show the reaction diagram
racemase and dehydratase reaction mechanism of serine racemase, overview
-
SYSTEMATIC NAME
IUBMB Comments
serine racemase
A pyridoxal-phosphate protein that is highly selective for L-serine as substrate. D-Serine is found in type-II astrocytes in mammalian brain, where it appears to be an endogenous ligand of the glycine site of N-methyl-D-aspartate (NMDA) receptors [1,2]. The reaction can also occur in the reverse direction but does so more slowly at physiological serine concentrations [4].
CAS REGISTRY NUMBER
COMMENTARY hide
77114-08-0
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
L-serine
D-serine
show the reaction diagram
D-serine
L-serine
show the reaction diagram
-
-
-
-
?
L-serine
D-serine
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
L-serine
D-serine
show the reaction diagram
L-serine
D-serine
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
pyridoxal 5'-phosphate
-
-
pyridoxal 5'-phosphate
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Mg2+
-
activates
Mg2+
-
activates
additional information
-
the enzyme is activated by divalent cations
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
amino-oxyacetic acid
-
-
hydroxylamine
-
-
phosphatidylinositol-4,5-bisphosphate
-
-
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
ATP
-
activates
morphine
-
chronic administration significantly augments both serine racemase mRNA and protein expression in all brain regions and leads to slight but significant elevation in the concentration of D-serine in the cortex, striatum, and hippocampus
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
60
D-serine
-
pH 8.0, 37°C
10
L-serine
-
pH 8.0, 37°C
additional information
additional information
-
kinetic analysis
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.083
-
pH 8.0, 37°C
additional information
-
D-serine concentration in brain areas, overview
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
8
-
assay at
7
-
10% of maximum activity
9
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
a retinal Mueller cell line, enzyme expression analysis, uptake of D-serine in Mueller cells is specific for neutral amino acids and excludes anionic and cationic amino acids, specificity and activity of transporters, overview
Manually annotated by BRENDA team
-
of optic nerve
Manually annotated by BRENDA team
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mRNA is ubiquitously expressed in all cell layers of proliferating to hypertrophic chondrocytes
Manually annotated by BRENDA team
-
vestibular sensory epithelium, in transitional cells therein, which are parasensory cells located between the sensory epithelium and the dark cells, and in dark cells
Manually annotated by BRENDA team
-
a microglial cell line
Manually annotated by BRENDA team
-
Schwann cell and other endoneural components of spinal nerve, lysates of sciatic nerve
Manually annotated by BRENDA team
-
head of optic nerve
Manually annotated by BRENDA team
-
of neonatal rat, mRNA is ubiquitously expressed in all cell layers of proliferating to hypertrophic chondrocytes
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
high amount of the enzyme
Manually annotated by BRENDA team
-
high amount of the enzyme
Manually annotated by BRENDA team
additional information
-
enzyme translocation to the membrane is blocked by a palmitoylation inhibitor, indicating that membrane binding is mediated by fatty acid acylation of the enzyme
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
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
physiological function
physiological function
additional information
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
Sequence
SRR_RAT
333
0
35693
Swiss-Prot
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
38000
37000
-
x * 37000, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
nitrosylation
-
S-nitrosylation inhibits racemase activity
phospholipoprotein
-
the enzyme is acylated in transfected neuroblastoma cells through the formation of an oxyester bond with serine or threonine residues using palmitate or octanoic acid as precursors. Phosphorylation of Thr227 is also required for steady-state binding of the enzyme to the membrane under basal, nonstimulated condition. No S-palmitoylation of the enzyme in SH-SY5Y neuroblastoma cells, but O-palmitoylation
phosphoprotein
-
serine racemase can be activated by phosphorylation
CRYSTALLIZATION/commentary
ORGANISM
UNIPROT
LITERATURE
purified recombinant mutant C2D/C6D by sitting drop vapor diffusion, 35 mg/ml protein, from 55% v/v Tacsimate, i.e. 1.8305 M malonic acid, 0.25 M ammonium citrate tribasic, 0.12 M succinic acid, 0.3 M DL-malic acid, 0.4 M sodium acetate trihydrate, 0.5 M sodium formate, and 0.16 M ammonium tartrate dibasic, pH 8.0, and 100 mM Bis-Tris propane, pH 7.8, 10 days, X-ray diffraction structure determination and analysis at 1.8-1.95 A resolution
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C2D/C6D
-
site-directed mutagenesis
additional information
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
4°C, stable for at least 4 days
-
PURIFICATION/commentary
ORGANISM
UNIPROT
LITERATURE
recombinant His-tagged wild-type enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography and dialysis
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recombinant His-tagged enzyme mutant from Escherichia coli strain Rosetta 2 (DE3) by affinity chromatography and gel filtration to over 98% purity
-
CLONED/commentary
ORGANISM
UNIPROT
LITERATURE
gene Srr, DNA and amino acid sequence determination and analysis, the single guide (sg) RNA target sequence in the exon 4 of Srr are annealed and subcloned into the BsbI site of pX362 to yield the pXSrre4T1, the circular pXSrre4T1 plasmid is transfected into PC-12 cells, recombinant expression of His-tagged wild-type enzyme in Escherichia coli strain BL21(DE3)
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total RNA is isolated from rMC-1 cells reverse-transcribed into cDNA and subjected to PCR using rat-specific SR primers, expression analysis of the enzyme in retinal Mueller cells
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expression of His-tagged enzyme mutant in Escherichia coli strain Rosetta 2 (DE3)
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overexpression in ATDC5 cell and in COS7 cell
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overexpression of HA-tagged enzyme in SH-SY5Y neuroblastoma cells and in HEK293 cells, coexpression with palmitic acid leads to acylation of the enzyme
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
L-serine or D-serine, but not D-proline, increase the expression of SRR in C6 cells when added to the cell culture medium
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
drug development
-
the enzyme and enzyme mutants may serve as targets for future docking studies and drug design
drug development
-
serine racemase is a promising target for the development of specific inhibitors in the treatment of disorders related to NMDAR dysfunction. Analysis of the molecular basis for rational drug design using the X-ray crystal structures of human and rat serine racemase
medicine
-
elevated levels of enzyme mRNA in Alzheimer´s disease hippocampus
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Wu, S.; Barger, S.W.; Sims, T.J.
Schwann cell and epineural fibroblast expression of serine racemase
Brain Res.
1020
161-166
2004
Rattus norvegicus
Manually annotated by BRENDA team
Wu, S.Z.; Bodles, A.M.; Porter, M.M.; Griffin, W.S.; Basile, A.S.; Barger, S.W.
Induction of serine racemase expression and D-serine release from microglia by amyloid beta-peptide
J. Neuroinflammation
1
2
2004
Rattus norvegicus
Manually annotated by BRENDA team
Dememes, D.; Mothet, J.P.; Nicolas, M.T.
Cellular distribution of d-serine, serine racemase and d-amino acid oxidase in the rat vestibular sensory epithelia
Neuroscience
137
991-997
2006
Rattus norvegicus
Manually annotated by BRENDA team
Stevens, E.R.; Esguerra, M.; Kim, P.M.; Newman, E.A.; Snyder, S.H.; Zahs, K.R.; Miller, R.F.
D-serine and serine racemase are present in the vertebrate retina and contribute to the physiological activation of NMDA receptors
Proc. Natl. Acad. Sci. USA
100
6789-6794
2003
Ambystoma tigrinum, Mus musculus, Rattus norvegicus
Manually annotated by BRENDA team
Wolosker, H.; Sheth, K.N.; Takahashi, M.; Mothet, J.P.; Brady, R.O., Jr.; Ferris, C.D.; Snyder, S.H.
Purification of serine racemase: biosynthesis of the neuromodulator D-serine
Proc. Natl. Acad. Sci. USA
96
721-725
1999
Rattus norvegicus
Manually annotated by BRENDA team
Wu, S.; Basile, A.S.; Barger, S.W.
Induction of serine racemase expression and D-serine release from microglia by secreted amyloid precursor protein (sAPP)
Curr. Alzheimer Res.
4
243-251
2007
Homo sapiens (Q9GZT4), Rattus norvegicus
Manually annotated by BRENDA team
Takeyama, K.; Yoshikawa, M.; Oka, T.; Kawaguchi, M.; Suzuki, T.; Hashimoto, A.
Ketamine enhances the expression of serine racemase and D-amino acid oxidase mRNAs in rat brain
Eur. J. Pharmacol.
540
82-86
2006
Rattus norvegicus
Manually annotated by BRENDA team
Hashimoto, A.; Yoshikawa, M.; Andoh, H.; Yano, H.; Matsumoto, H.; Kawaguchi, M.; Oka, T.; Kobayashi, H.
Effects of MK-801 on the expression of serine racemase and D-amino acid oxidase mRNAs and on the D-serine levels in rat brain
Eur. J. Pharmacol.
555
17-22
2007
Rattus norvegicus
Manually annotated by BRENDA team
Dun, Y.; Mysona, B.; Itagaki, S.; Martin-Studdard, A.; Ganapathy, V.; Smith, S.B.
Functional and molecular analysis of D-serine transport in retinal Mueller cells
Exp. Eye Res.
84
191-199
2007
Rattus norvegicus (Q76EQ0)
Manually annotated by BRENDA team
Yoshikawa, M.; Shinomiya, T.; Takayasu, N.; Tsukamoto, H.; Kawaguchi, M.; Kobayashi, H.; Oka, T.; Hashimoto, A.
Long-term treatment with morphine increases the D-serine content in the rat brain by regulating the mRNA and protein expressions of serine racemase and D-amino acid oxidase
J. Pharmacol. Sci.
107
270-276
2008
Rattus norvegicus (Q76EQ0)
Manually annotated by BRENDA team
Takayasu, N.; Yoshikawa, M.; Watanabe, M.; Tsukamoto, H.; Suzuki, T.; Kobayashi, H.; Noda, S.
The serine racemase mRNA is expressed in both neurons and glial cells of the rat retina
Arch. Histol. Cytol.
71
123-129
2008
Rattus norvegicus (Q76EQ0)
Manually annotated by BRENDA team
Takarada, T.; Hinoi, E.; Takahata, Y.; Yoneda, Y.
Serine racemase suppresses chondrogenic differentiation in cartilage in a Sox9-dependent manner
J. Cell. Physiol.
215
320-328
2008
Rattus norvegicus
Manually annotated by BRENDA team
Smith, M.A.; Mack, V.; Ebneth, A.; Moraes, I.; Felicetti, B.; Wood, M.; Schonfeld, D.; Mather, O.; Cesura, A.; Barker, J.
The structure of mammalian serine racemase: evidence for conformational changes upon inhibitor binding
J. Biol. Chem.
285
12873-12881
2010
Homo sapiens, Homo sapiens (Q9GZT4), Rattus norvegicus
Manually annotated by BRENDA team
Sikka, P.; Walker, R.; Cockayne, R.; Wood, M.J.; Harrison, P.J.; Burnet, P.W.
D-Serine metabolism in C6 glioma cells: Involvement of alanine-serine-cysteine transporter (ASCT2) and serine racemase (SRR) but not D-amino acid oxidase (DAO)
J. Neurosci. Res.
88
1829-1840
2010
Rattus norvegicus (Q76EQ0)
Manually annotated by BRENDA team
Balan, L.; Foltyn, V.N.; Zehl, M.; Dumin, E.; Dikopoltsev, E.; Knoh, D.; Ohno, Y.; Kihara, A.; Jensen, O.N.; Radzishevsky, I.S.; Wolosker, H.
Feedback inactivation of D-serine synthesis by NMDA receptor-elicited translocation of serine racemase to the membrane
Proc. Natl. Acad. Sci. USA
106
7589-7594
2009
Rattus norvegicus
Manually annotated by BRENDA team
Ohide, H.; Miyoshi, Y.; Maruyama, R.; Hamase, K.; Konno, R.
D-Amino acid metabolism in mammals: biosynthesis, degradation and analytical aspects of the metabolic study
J. Chromatogr. B
879
3162-3168
2011
Homo sapiens, Mus musculus, Rattus norvegicus
Manually annotated by BRENDA team
Nitoker, N.; Major, D.T.
Understanding the reaction mechanism and intermediate stabilization in mammalian serine racemase using multiscale quantum-classical simulations
Biochemistry
54
516-527
2015
Homo sapiens, Homo sapiens (Q9GZT4), Rattus norvegicus (Q76EQ0)
Manually annotated by BRENDA team
Ito, T.; Hayashida, M.; Kobayashi, S.; Muto, N.; Hayashi, A.; Yoshimura, T.; Mori, H.
Serine racemase is involved in D-aspartate biosynthesis
J. Biochem.
160
345-353
2016
Mus musculus (Q9QZX7), Rattus norvegicus (Q76EQ0)
Manually annotated by BRENDA team
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