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Information on EC 5.1.1.18 - serine racemase and Organism(s) Schizosaccharomyces pombe and UniProt Accession O59791
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5.1.1.18 serine racemaseIUBMB 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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Word Map
- 5.1.1.18
- d-serine
- n-methyl-d-aspartate
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co-agonist
-
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
-
glutamatergic
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5'-phosphate-dependent
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nmda-type
- d-ser
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plp-dependent
-
nmdar-mediated
- pharmacology
- medicine
-
alanine-serine-cysteine
- drug development
-
glycine-binding
-
n-methyl-d
-
vante
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brain-enriched
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gliotransmitter
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nmdar-dependent
The taxonomic range for the selected organisms is: Schizosaccharomyces pombe
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
serine racemase, srace, t01h8.2, ser racemase, 
more
topREACTION 
REACTION DIAGRAM
COMMENTARY 
ORGANISM
UNIPROT
LITERATURE
L-serine = D-serine
two-base racemization mechanism, overview. The enzyme utilizes a two-base mechanism wherein one enantiospecific Broensted base abstracts the proton from the L-Ser-pyridoxal 5'-phosphate aldimine and the conjugate acid of a second enantiospecific Bronsted base protonates the intermediate to form the D-Ser-pyridoxal 5'-phosphate aldimine, and vice versa
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L-serine = D-serine
substrate recognition mechanism and catalytic mechanisms of both reactions, the racemization and the dehydration of serine, residues Lys57 and Ser82 located on the protein and solvent sides, respectively, with respect to the cofactor plane, are acid-base catalysts that shuttle protons to the substrate. Racemization mechanism via carbanion intermediate, alpha-aminoacrylate intermediate, and pyridoxal 5'-phosphate-lysine-D-alanine Schiff base
PATHWAY SOURCE
PATHWAYS
BRENDA
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-, -
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
77114-08-0
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
L-serine
D-serine
on binding of the substrate, the small domain rotates toward the large domain to close the active site, substrate binding structure, Lys57 is the catalytic residue of the wild-type enzyme, overview
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r
additional information
?
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the enzyme also catalyzes the dehydration of D- and L-serine resulting in pyruvate
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-
?
additional information
?
-
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the enzyme also catalyzes the dehydration of D- and L-serine resulting in pyruvate
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-
?
additional information
?
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the enzyme catalyzes both the racemization and alpha,beta-elimination reaction of L- and D-serine to yield pyruvate and ammonia
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?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
additional information
?
-
-
the enzyme catalyzes both the racemization and alpha,beta-elimination reaction of L- and D-serine to yield pyruvate and ammonia
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-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
pyridoxal 5'-phosphate
dependent on, binding structure, overview
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
AMP-PCP
Mg-AMP-PCP is bound to the groove formed at the intersection between the domain interface and the subunit interface, structure and binding mode, overview. The binding of Mg-AMP-PCP to the enzyme in the open form does not induce a subunit conformational change, but, interestingly, changes the relative orientation between the two subunits
alpha-(hydroxymethyl)-L-serine
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substrate-product analogue, a modest, linear mixed-type inhibitor of serine racemase
additional information
-
substrate-product analogue inhibitors of racemases may only be effective when the active site is capacious and/or plastic, or when the inhibitor is sufficiently flexible
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ATP
as MgATP2-, the ATP binding site is located at the domain and the subunit interface
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
167
alpha-(hydroxymethyl)-L-serine
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pH and temperature not specified in the publication
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
PDB
SCOP
CATH
UNIPROT
ORGANISM
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
enzyme monomer and dimer structures, three-dimensional structure, overview. Structural model of external aldimine of the wild-type enzyme
additional information
-
enzyme monomer and dimer structures, three-dimensional structure, overview. Structural model of external aldimine of the wild-type enzyme
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
free wild-type enzyme, wild-type enzyme in complex with the ATP analogue AMP-PCP, and the modified enzyme in complex with serine, vapor diffusion method at 20°C, 0.003 ml of protein solution with 2.2 mg/ml protein and 10 mM Tris-HCl buffer, pH 8.0, are mixed with an equal volume of reservoir solution containing 28% w/v PEG 4000, 200 mM sodium acetate, and 100 mM Tris-HCl, pH 8.5, and equilibrated against 450 ml of the reservoir solution, for the ligand complexed enzyme, 10 mM AMP-PCP and 0.2 M MgCl2 are added, X-ray diffraction structure determination and analysis at at 1.7 A, 1.9 A, and 2.2 A resolution, respectively
native and modified enzyme, X-ray diffraction structure determination and analysis at 1.7 A resolution
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
construction of a modified enzyme, which has a unique lysino-D-alanyl residue at the active site, and also exhibits catalytic activities. The substrate serine is actually trapped in the active site of the modified enzyme, suggesting that the lysino-D-alanyl residue acts as a catalytic base in the same manner as inherent Lys57 of the wild-type enzyme
additional information
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construction of a modified enzyme, which has a unique lysino-D-alanyl residue at the active site, and also exhibits catalytic activities. The substrate serine is actually trapped in the active site of the modified enzyme, suggesting that the lysino-D-alanyl residue acts as a catalytic base in the same manner as inherent Lys57 of the wild-type enzyme
additional information
the yeast enzyme is covalently modified with dehydroalanine derived from its natural substrate serine, giving a serine racemase with catalytically active lysinoalanyl residue. The modification is not reversed by incubation in 20 mM potassium phosphate buffer, pH 7.2, without serine for several days at room temperature. The enzyme remains partially active even though its essential Lys57 inherently forming a Schiff base with the coenzyme pyridoxal 5'-phosphate is converted to N(6)-(R-2-amino-2-carboxyethyl)-L-lysyl (lysino-D-alanyl) residue. The alpha-amino group of the D-alanyl moiety of the lysino-D-alanyl residue serves as a catalytic base in the same manner asthe epsilon-amino group of Lys57 of the original enzyme. The specific activities of modified spSR for L-serine racemization and L-serine dehydration are 54%, and 68%, respectively, of those of the original spSR
additional information
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the yeast enzyme is covalently modified with dehydroalanine derived from its natural substrate serine, giving a serine racemase with catalytically active lysinoalanyl residue. The modification is not reversed by incubation in 20 mM potassium phosphate buffer, pH 7.2, without serine for several days at room temperature. The enzyme remains partially active even though its essential Lys57 inherently forming a Schiff base with the coenzyme pyridoxal 5'-phosphate is converted to N(6)-(R-2-amino-2-carboxyethyl)-L-lysyl (lysino-D-alanyl) residue. The alpha-amino group of the D-alanyl moiety of the lysino-D-alanyl residue serves as a catalytic base in the same manner asthe epsilon-amino group of Lys57 of the original enzyme. The specific activities of modified spSR for L-serine racemization and L-serine dehydration are 54%, and 68%, respectively, of those of the original spSR
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Yamauchi, T.; Goto, M.; Wu, H.Y.; Uo, T.; Yoshimura, T.; Mihara, H.; Kurihara, T.; Miyahara, I.; Hirotsu, K.; Esaki, N.
Serine racemase with catalytically active lysinoalanyl residue
J. Biochem.
145
421-424
2009
Schizosaccharomyces pombe (O59791), Schizosaccharomyces pombe
Goto, M.; Yamauchi, T.; Kamiya, N.; Miyahara, I.; Yoshimura, T.; Mihara, H.; Kurihara, T.; Hirotsu, K.; Esaki, N.
Crystal structure of a homolog of mammalian serine racemase from Schizosaccharomyces pombe
J. Biol. Chem.
284
25944-25952
2009
Schizosaccharomyces pombe (O59791), Schizosaccharomyces pombe
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Release 2023.1 (January 2023)
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