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Information on EC 2.1.2.1 - glycine hydroxymethyltransferase and Organism(s) Oryctolagus cuniculus and UniProt Accession P07511
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2.1.2.1 glycine hydroxymethyltransferaseIUBMB Comments
A pyridoxal-phosphate protein. Also catalyses the reaction of glycine with acetaldehyde to form L-threonine, and with 4-trimethylammoniobutanal to form 3-hydroxy-N6,N6,N6-trimethyl-L-lysine.
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Word Map
- 2.1.2.1
-
one-carbon
- pyridoxal
- thymidylate
- purine
- 5'-phosphate
- homocysteine
- dihydrofolate
-
folate-dependent
-
photorespiratory
-
photorespiration
-
folate-mediated
- pyridoxal-5'-phosphate
- thf
- dtmp
- mthfd1
-
plp-dependent
-
remethylation
-
aldimine
- phgdh
- medicine
-
folate-metabolizing
- 5,10-methenyltetrahydrofolate
-
5'-phosphate-dependent
- antifolate
- hydroxypyruvate
-
quinonoid
- 5-methyltetrahydrofolate
- glycerate
- 5-formyltetrahydrofolate
- drug development
-
folate-related
- d-alanine
-
c1-tetrahydrofolate
-
1-carbon
-
5-formyl
- polyglutamate
- l-threonine
-
alpha-protons
-
slc19a1
-
retro-aldol
- degradation
- analysis
- synthesis
- biotechnology
- pharmacology
The taxonomic range for the selected organisms is: Oryctolagus cuniculus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
serine hydroxymethyltransferase, shmt2, shmt1, serine hydroxymethyl transferase, serine transhydroxymethylase, serine hydroxymethyltransferase 2, mitochondrial serine hydroxymethyltransferase, serine hydroxymethyltransferase 1, bsshmt, pvshmt, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
L-serine hydroxymethyltransferase
-
-
-
-
serine hydroxymethylase hydroxymethyltransferase, serine
-
-
-
-
serine hydroxymethyltransferase
serine transhydroxymethylase
-
-
-
-
serine hydroxymethyltransferase
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
5,10-methylenetetrahydrofolate + glycine + H2O = tetrahydrofolate + L-serine
mechanism
-
5,10-methylenetetrahydrofolate + glycine + H2O = tetrahydrofolate + L-serine
stereochemistry
-
5,10-methylenetetrahydrofolate + glycine + H2O = tetrahydrofolate + L-serine
enzyme exhibits threonine aldolase activity (EC 4.1.2.5), but the two enzymes are distinct
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydroxymethyl group transfer
-
-
-
-
PATHWAY SOURCE
PATHWAYS
KEGG
-
-, -, -, -, -, -, -, -, -, -, -, -, -, -
SYSTEMATIC NAME
IUBMB Comments
5,10-methylenetetrahydrofolate:glycine hydroxymethyltransferase
A pyridoxal-phosphate protein. Also catalyses the reaction of glycine with acetaldehyde to form L-threonine, and with 4-trimethylammoniobutanal to form 3-hydroxy-N6,N6,N6-trimethyl-L-lysine.
CAS REGISTRY NUMBER
COMMENTARY
9029-83-8
-
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
5,10-methenyl-tetrahydropteroyl pentaglutamate + glycine + H2O
5-formyl-tetrahydropteroyl pentaglutamate + L-serine
-
-
-
?
L-Ser + tetrahydrofolate
Gly + 5,10-methylenetetrahydrofolate
-
-
-
?
L-serine + tetrahydrofolate
glycine + 5,10-methylenetetrahydrofolate + H2O
-
-
-
?
5,10-methylenetetrahydrofolate + glycine + H2O
tetrahydrofolate + L-serine
-
-
-
-
?
5,10-methylenetetrahydrofolate + glycine + H2O
tetrahydrofolate + L-serine
-
-
-
-
r
5,10-methylenetetrahydrofolate + glycine + H2O
tetrahydrofolate + L-serine
-
tetrahydrofolate-dependent SHMT activity, modeling of substrate binding, overview
-
-
?
alpha-methylserine + tetrahydrofolate
D-alanine + 5,10-methylenetetrahydrofolate
-
-
-
?
alpha-methylserine + tetrahydrofolate
D-alanine + 5,10-methylenetetrahydrofolate
-
-
-
?
alpha-methylserine + tetrahydrofolate
D-alanine + 5,10-methylenetetrahydrofolate
-
-
-
?
alpha-methylserine + tetrahydrofolate
D-alanine + 5,10-methylenetetrahydrofolate
-
at high concentrations of enzyme
-
?
L-serine + tetrahydrofolate
glycine + 5,10-methylenetetrahydrofolate + H2O
-
-
-
?
L-serine + tetrahydrofolate
glycine + 5,10-methylenetetrahydrofolate + H2O
-
-
-
?
L-serine + tetrahydrofolate
glycine + 5,10-methylenetetrahydrofolate + H2O
-
-
-
-
?
L-serine + tetrahydrofolate
glycine + 5,10-methylenetetrahydrofolate + H2O
-
-
-
?
L-serine + tetrahydrofolate
glycine + 5,10-methylenetetrahydrofolate + H2O
-
-
-
r
L-serine + tetrahydrofolate
glycine + 5,10-methylenetetrahydrofolate + H2O
-
-
-
r
L-serine + tetrahydrofolate
glycine + 5,10-methylenetetrahydrofolate + H2O
-
-
-
-
r
L-serine + tetrahydrofolate
glycine + 5,10-methylenetetrahydrofolate + H2O
-
-
-
r
L-serine + tetrahydrofolate
glycine + 5,10-methylenetetrahydrofolate + H2O
-
-
-
r
L-serine + tetrahydrofolate
glycine + 5,10-methylenetetrahydrofolate + H2O
-
-
-
r
L-serine + tetrahydrofolate
glycine + 5,10-methylenetetrahydrofolate + H2O
-
-
-
-
r
L-serine + tetrahydrofolate
glycine + 5,10-methylenetetrahydrofolate + H2O
-
-
-
r
L-serine + tetrahydrofolate
glycine + 5,10-methylenetetrahydrofolate + H2O
-
enzyme is a component of thymidylate cycle
-
?
L-serine + tetrahydrofolate
glycine + 5,10-methylenetetrahydrofolate + H2O
-
may play important role in central nervous system
-
?
L-serine + tetrahydrofolate
glycine + 5,10-methylenetetrahydrofolate + H2O
-
catalyzes interconversion of serine and glycine
-
?
L-serine + tetrahydrofolate
glycine + 5,10-methylenetetrahydrofolate + H2O
-
enzyme plays a pivotal role in channelling metabolites between amino acid and nucleotide metabolism
-
?
additional information
?
-
-
review and comparison of enzyme activity, threonine aldolase and allothreonine aldolase activity from various sources
-
-
?
additional information
?
-
-
enzyme transaminates D-alanine to pyruvate and pyridoxamine phosphate
-
-
?
additional information
?
-
-
enzyme transaminates D-alanine to pyruvate and pyridoxamine phosphate
-
-
?
additional information
?
-
-
enzyme transaminates D-alanine to pyruvate and pyridoxamine phosphate
-
-
?
additional information
?
-
-
the enzyme also exhibits tetrahydrofolate-independent aldolase activity, EC 4.1.2.5, toward beta-hydroxyamino acids, producing glycine and aldehydes
-
-
?
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
5,10-methylenetetrahydrofolate + glycine + H2O
tetrahydrofolate + L-serine
-
-
-
-
?
L-serine + tetrahydrofolate
glycine + 5,10-methylenetetrahydrofolate + H2O
-
-
-
?
L-serine + tetrahydrofolate
glycine + 5,10-methylenetetrahydrofolate + H2O
-
-
-
?
L-serine + tetrahydrofolate
glycine + 5,10-methylenetetrahydrofolate + H2O
-
enzyme is a component of thymidylate cycle
-
?
L-serine + tetrahydrofolate
glycine + 5,10-methylenetetrahydrofolate + H2O
-
may play important role in central nervous system
-
?
L-serine + tetrahydrofolate
glycine + 5,10-methylenetetrahydrofolate + H2O
-
catalyzes interconversion of serine and glycine
-
?
L-serine + tetrahydrofolate
glycine + 5,10-methylenetetrahydrofolate + H2O
-
enzyme plays a pivotal role in channelling metabolites between amino acid and nucleotide metabolism
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
pyridoxal 5'-phosphate
-
requirement, 4 mol per mol enzyme
pyridoxal 5'-phosphate
-
one mol/subunit bound to the epsilon-amino group of lysine
pyridoxal 5'-phosphate
-
important role in maintaining the structural integrity of the enzyme by preventing the dissociation of the enzyme into subunits, in addition to its function in catalysis
tetrahydrofolate
-
requirement with L-serine or L-2-methylserine as substrate
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Antibodies to mitochondrial enzyme
-
no inhibition of cytosolic enzyme
-
Bromopyruvate
-
irreversible inactivation, substrates partially protect
Chloroacetaldehyde
-
irreversible inactivation, substrates partially protect
iodoacetamide
-
irreversible inactivation, substrates partially protect
additional information
-
not: purine nucleoside mono-, di- and triphosphates
-
additional information
-
not: NaN3, mono- or divalent cations, 2-mercaptoethanol, DTT
-
additional information
-
not: N-/O-chloroacetyl and N-/O-bromoacetyl derivatives of glycine and L-serine
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
pH-dependence of kinetic parameters
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.033
tetrahydrofolate
mutant L474F, in the presence of pyridoxal phosphate
0.045
tetrahydrofolate
mutant S394N, in the presence of pyridoxal phosphate
0.07
tetrahydrofolate
wild-type, in the presence of pyridoxal phosphate
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
comparison of Ki for allothreonine and threonine
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6 - 8.5
-
cytosol: about 60% of maximal activity at pH 6, about 70% at 8.5, mitochondria: about 40% of maximal activity at pH 6.0 and 8.5
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
-
additional information
additional information
-
comparison of cytosolic and mitochondrial forms of enzyme
-
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). GLYC_RABIT
484
0
52975
Swiss-Prot
other Location (Reliability: 2)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
homotetramer
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
side-chain modification
-
in addition to the lysine residue involved in Schiff base formation with the PLP, other residues like arginine, histidine, cysteine and tryptophan essential for catalysis, review
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
hanging-drop vapour diffusion technique. Crystals of both mutants, E75L and E75Q are obtained by mixing 0.003v ml of an enzyme solution (34-44 mg/ml in 20 mM potassium phosphate, pH 7.3, with 1 mM dithiothreitol) with an equal volume of reservoir solution. The reservoir solution for E75L rcSHMT consists of 50 mM potassium phosphate, pH 6.6, 8.5-9.1% PEG 8000, and 100 mM KCl. For E75Q rcSHMT the reservoir solution consists of 15 mM potassium 2-(N-morpholino)ethanesulfonate, pH 6.4, 8.5-10% PEG 4000, and 30 mM KCl. Serine complexes are formed by adding 0.00025 ml of 250 mM L-serine directly to the drop
crystal structure at 2.7 A resolution of the recombinant enzyme with active-site bound 5-formyl-tetrahydropteroylglutamate is obtained by soaking unliganded crystals of of the recombinant enzyme in 5-formyl-tetrahydropteroylglutamate, the conformation of the pteridine ring and its interactions with the enzyme differ slightly from those observed in complexes of the monoglutamate cofactor
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
E75L
no activity with L-Ser and tetrahydrofolate. The mutant enzyme does not catalyze the formation of 5,10-methenyl-tetrahydropteroylglutamate or N5-hydroxymethylene-tetrahydropteroylglutamate
E75Q
500fold decrease in activity with L-Ser and tetrahydrofolate compared to wild-type enzyme, the KM-value for L-allothreonine is 10fold increased compared to wild-type value, the turnover-number for reaction with L-allothreonine is 4.3fold increased compared to wild-type enzyme
L474F
shows normal values for kcat and Km for serine, shows lowered affinity (increased dissociation constant) for only the pentaglutamate form of the folate ligand, shows decreased rates of pyridoxal phosphate addition to the mutant apo enzymes to form the active holo enzymes, thermal stability of SHMT or the rate at which it converts 5,10-methenyl tetrahydropteroyl pentaglutamate to 5-formyl tetrahydropteroyl pentaglutamate not affected
S394N
shows normal values for kcat and Km for serine, has increased dissociation constant values for both glycine and tetrahydrofolate and its pentaglutamate form compared to wild-type enzyme, shows decreased rates of pyridoxal phosphate addition to the mutant apo enzymes to form the active holo enzymes, thermal stability of SHMT or the rate at which it converts 5,10-methenyl tetrahydropteroyl pentaglutamate to 5-formyl tetrahydropteroyl pentaglutamate not affected
E75L
-
site-directed mutagenesis, mutation of a substrate binding residue, the mutant retains tetrahydrofolate-independent aldolase activity
E75Q
-
site-directed mutagenesis, mutation of a substrate binding residue, the mutant retains tetrahydrofolate-independent aldolase activity
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
by ammonium sulfate precipitation and gel filtration, more than 95% pure
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
mutations introduced into the cDNA for rabbit cytosolic SHMT and expressed from an Escherichia coli expression system
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
-
enzyme is a potential target for cancer chemotherapy
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Schirch, L.; Peterson, D.
Purification and properties of mitochondrial serine hydroxymethyltransferase
J. Biol. Chem.
255
7801-7806
1980
Oryctolagus cuniculus
Schirch, L.; Gross, T.
Serine transhydroxymethylase. Identification as the threonine and allothreonine aldolases
J. Biol. Chem.
243
5651-5655
1968
Oryctolagus cuniculus
Fujioka, M.
Purification and properties of serine hydroxymethylase from soluble and mitochondrial fractions of rabbit liver
Biochim. Biophys. Acta
185
338-349
1969
Oryctolagus cuniculus
Akhtar, M.; El-Obeid, H.A.
Interaction of serine transhydroxymethylase and threonine aldolase activities
Biochim. Biophys. Acta
791
791-799
1972
Oryctolagus cuniculus
-
El-Obeid, H.A.; Akhtar, M.
Glycidaldehyde, an inhibitor directed towards the C1-units-binding site of serine transhydoxymethylase
Biochem. Soc. Trans.
1
1274-1276
1973
Oryctolagus cuniculus
-
Stover, P.; Schirch, V.
5-Formyltetrahydrofolate polyglutamates are slow tight binding inhibitors of serine hydroxymethyltransferase
J. Biol. Chem.
266
1543-1550
1991
Oryctolagus cuniculus, Escherichia coli
Akhtar, M.; El-Obeida, H.A.; Jordan, P.M.
Mechanistic, inhibitory and stereochemical studies on cytoplasmic and mitochondrial serine transhydorxymethylases
Biochem. J.
145
159-168
1975
Oryctolagus cuniculus
Schirch, L.
Serine hydroxymethyltransferase
Adv. Enzymol. Relat. Areas Mol. Biol.
53
83-112
1982
Bos taurus, Saccharomyces cerevisiae, Cricetulus griseus, Oryctolagus cuniculus, Ovis aries, Neurospora crassa, Salmonella enterica subsp. enterica serovar Typhimurium
Di Salvo, M.L.; Delle Fratte, S.; De Biase, D.; Bossa, F.; Schirch, V.
Purification and characterization of recombinant rabbit cytosolic serine hydroxymethyltransferase
Protein Expr. Purif.
13
177-183
1998
Oryctolagus cuniculus
Appaji Rao, N.; Talwar, R.; Savithri, H.S.
Molecular organization, catalytic mechanism and function of serine hydroxymethyltransferase - a potential target for cancer chemotherapy
Int. J. Biochem. Cell Biol.
32
405-416
2000
Saccharomyces cerevisiae, Oryctolagus cuniculus, Escherichia coli, Ovis aries, Homo sapiens, Pisum sativum
Ogawa, H.; Gomi, T.; Fujioka, M.
Serine hydroxymethyltransferase and threonine aldolase: are they identical?
Int. J. Biochem. Cell Biol.
32
289-301
2000
Cricetulus griseus, Escherichia coli, Homo sapiens, Neurospora crassa, Oryctolagus cuniculus, Ovis aries, Pisum sativum, Rattus norvegicus, Vigna radiata
Szebenyi, D.M.; Musayev, F.N.; di Salvo, M.L.; Safo, M.K.; Schirch, V.
Serine hydroxymethyltransferase: role of Glu75 and evidence that serine is cleaved by a retroaldol mechanism
Biochemistry
43
6865-6876
2004
Oryctolagus cuniculus (P07511)
Fu, T.F.; Scarsdale, J.N.; Kazanina, G.; Schirch, V.; Wright, H.T.
Location of the pteroylpolyglutamate-binding site on rabbit cytosolic serine hydroxymethyltransferase
J. Biol. Chem.
278
2645-2653
2003
Oryctolagus cuniculus
Fu, T.F.; Hunt, S.; Schirch, V.; Safo, M.K.; Chen, B.H.
Properties of human and rabbit cytosolic serine hydroxymethyltransferase are changed by single nucleotide polymorphic mutations
Arch. Biochem. Biophys.
442
92-101
2005
Homo sapiens, Oryctolagus cuniculus (P07511), Oryctolagus cuniculus
Siglioccolo, A.; Bossa, F.; Pascarella, S.
Structural adaptation of serine hydroxymethyltransferase to low temperatures
Int. J. Biol. Macromol.
46
37-46
2010
Geobacillus stearothermophilus, Oryctolagus cuniculus, Escherichia coli, Homo sapiens, Mus musculus
Chiba, Y.; Terada, T.; Kameya, M.; Shimizu, K.; Arai, H.; Ishii, M.; Igarashi, Y.
Mechanism for folate-independent aldolase reaction catalyzed by serine hydroxymethyltransferase
FEBS J.
279
504-514
2012
Geobacillus stearothermophilus, Oryctolagus cuniculus, Ovis aries, Hydrogenobacter thermophilus, Hydrogenobacter thermophilus TK-6 / IAM 12695
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