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Enzyme Nomenclature
Information on EC 2.1.2.10 - aminomethyltransferase
Word Map on EC 2.1.2.10
- 2.1.2.10
- hyperglycinemia
-
nonketotic
-
photorespiratory
-
ketotic
-
photorespiration
- dimethylglycine
-
hydroxymethyltransferase
- lipoamide
- h-protein
- medicine
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The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
topEC NUMBER 
COMMENTARY 
2.1.2.10
-
RECOMMENDED NAME
GeneOntology No.
aminomethyltransferase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
[protein]-S8-aminomethyldihydrolipoyllysine + tetrahydrofolate = [protein]-dihydrolipoyllysine + 5,10-methylenetetrahydrofolate + NH3
[protein]-S8-aminomethyldihydrolipoyllysine + tetrahydrofolate = [protein]-dihydrolipoyllysine + 5,10-methylenetetrahydrofolate + NH3
-
-
-
-
[protein]-S8-aminomethyldihydrolipoyllysine + tetrahydrofolate = [protein]-dihydrolipoyllysine + 5,10-methylenetetrahydrofolate + NH3
formation of a folate-binding cavity via the interaction of enzyme with H-protein
-
[protein]-S8-aminomethyldihydrolipoyllysine + tetrahydrofolate = [protein]-dihydrolipoyllysine + 5,10-methylenetetrahydrofolate + NH3
tetrahydrofolate is bound near the center of the tripartite enzyme, lipoic acid is bound adjacent to the tetrahydrofolate binding pocket
-
[protein]-S8-aminomethyldihydrolipoyllysine + tetrahydrofolate = [protein]-dihydrolipoyllysine + 5,10-methylenetetrahydrofolate + NH3
5-methyltetrahydrofolate is bound in a kinked shape with the pteridine group deeply buried into the hydrophobic pocket ant the glutamyl group pointed to the C-terminal side surface. R292 interacts through water molecules with the folate polyglutamate tail
[protein]-S8-aminomethyldihydrolipoyllysine + tetrahydrofolate = [protein]-dihydrolipoyllysine + 5,10-methylenetetrahydrofolate + NH3
T-protein recognition of lipoyl protein substrate and reaction mechanism, overview. The reversible transfer of the methylene group between the lipoate and tetrahydrofolate proceeds through the electron relay-assisted iminium intermediate formation
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C-N bond cleavage
-
-
-
-
methyl group transfer
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
SYSTEMATIC NAME
IUBMB Comments
[protein]-S8-aminomethyldihydrolipoyllysine:tetrahydrofolate aminomethyltransferase (ammonia-forming)
A component, with EC 1.4.4.2 glycine dehydrogenase (decarboxylating) and EC 1.8.1.4, dihydrolipoyl dehydrogenanse, of the glycine cleavage system, formerly known as glycine synthase. The glycine cleavage system is composed of four components that only loosely associate: the P protein (EC 1.4.4.2), the T protein (EC 2.1.2.10), the L protein (EC 1.8.1.4) and the lipoyl-bearing H protein [3].
CAS REGISTRY NUMBER
COMMENTARY
37257-08-2
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
glycine encephalopathy (GCE) or nonketotic hyperglycinemia is an inborn error of glycine metabolism, inherited in an autosomal recessive manner due to a defect in any one of the four enzymes aminomethyltransferase (AMT), glycine decarboxylase (GLDC), glycine cleavage system protein-H (GCSH) and dehydrolipoamide dehydrogenase in the glycine cleavage system. This defect leads to glycine accumulation in body tissues, including the brain, and causes various neurological symptoms such as encephalopathy, hypotonia, apnea, intractable seizures and possible death, phenotypes, overview. Mutations in both GLDC and AMT genes are the main cause of glycine encephalopathy in Malaysian population
metabolism
-
aminomethyltransferase is a component of the T-protein, which is part of a multienzyme system composed of four proteins termed P-, H-, T-, and L-protein. T-protein/aminomethyltransferase degrades the aminomethyl moiety to ammonia and 5,10-methylentetrahydrofolate in the presence of tetrahydrofolate, leaving dihydrolipoate-bearing H-protein
physiological function
additional information
-
T-protein in complex with dihydrolipoate-bearing H-protein and 5-methyltetrahydrofolate, a complex mimicking the ternary complex in the reverse reaction, shows a highly interacting intermolecular interface limited to a small area and the protein-bound dihydrolipoyllysine arm inserted into the active site cavity of the T-protein. Arg292 of the T-protein is essential for complex assembly
physiological function
-
aminomethyltransferase reversibly catalyzes the degradation of the aminomethyl moiety of glycine attached to the lipoate cofactor of H-protein, resulting in the production of ammonia, 5,10-methylenetetrahydrofolate, and dihydrolipoate-bearing H-protein in the presence of tetrahydrofolate
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
reduced H-protein + 5,10-methylenetetrahydropteroyltetraglutamate + NH4Cl
?
-
-
-
-
?
S-aminomethyldihydrolipoylprotein + (6S)-tetrahydrofolate
dihydrolipoylprotein + (6R)-5,10-methylenetetrahydrofolate + NH3
S-aminomethyldihydrolipoylprotein + tetrahydropteroyltetraglutamate
dihydrolipoylprotein + 5,10-methylenetetrahydropteroyltetraglutamate + NH3
-
-
better substrate than 5,10-methylenetetrahydrofolate, 6.5fold higher affinity for 5,10-methylenetetrahydropteroyltetraglutamate than for 5,10-methylenetetrahydrofolate
?
[protein]-S8-aminomethyldihydrolipoyllysine + tetrahydrofolate
[protein]-dihydrolipoyllysine + 5,10-methylenetetrahydrofolate + NH3
-
-
-
-
r
S-aminomethyldihydrolipoylprotein + (6S)-tetrahydrofolate
dihydrolipoylprotein + (6R)-5,10-methylenetetrahydrofolate + NH3
-
aminomethyl intermediate bound to the lipoate cofactor of H-protein
-
r
S-aminomethyldihydrolipoylprotein + (6S)-tetrahydrofolate
dihydrolipoylprotein + (6R)-5,10-methylenetetrahydrofolate + NH3
-
T-protein catalyzes the tetrahydrofolate-dependent step of the glycine cleavage reaction
-
r
S-aminomethyldihydrolipoylprotein + (6S)-tetrahydrofolate
dihydrolipoylprotein + (6R)-5,10-methylenetetrahydrofolate + NH3
-
tetrahydrofolate-dependent enzyme
-
r
S-aminomethyldihydrolipoylprotein + (6S)-tetrahydrofolate
dihydrolipoylprotein + (6R)-5,10-methylenetetrahydrofolate + NH3
-
folate-binding site: Lys-78, Lys-81 and Lys-352 are involved in binding, Lys-352 may serve as the primary binding site to alpha-carboxyl group of the first glutamate residue nearest the p-aminobenzoic acid ring of 5,10-methylenetetrahydrofolate and 5,10-methylenetetrahydropteroyltetraglutamate, Lys-81 may play a key role to hold the second glutamate residue through binding to its alpha-carboxyl group, 6.5fold higher affinity for 5,10-methylenetetrahydropteroyltetraglutamate than for 5,10-methylenetetrahydrofolate
-
r
S-aminomethyldihydrolipoylprotein + (6S)-tetrahydrofolate
dihydrolipoylprotein + (6R)-5,10-methylenetetrahydrofolate + NH3
-
decarboxylated glycine moiety attached to H-protein + tetrahydrofolate as substrates
-
r
S-aminomethyldihydrolipoylprotein + (6S)-tetrahydrofolate
dihydrolipoylprotein + (6R)-5,10-methylenetetrahydrofolate + NH3
-
strictly dependent on tetrahydrofolate
-
r
S-aminomethyldihydrolipoylprotein + (6S)-tetrahydrofolate
dihydrolipoylprotein + (6R)-5,10-methylenetetrahydrofolate + NH3
-
part of the glycine cleavage system
-
-
?
S-aminomethyldihydrolipoylprotein + (6S)-tetrahydrofolate
dihydrolipoylprotein + (6R)-5,10-methylenetetrahydrofolate + NH3
-
-
-
-
?
S-aminomethyldihydrolipoylprotein + (6S)-tetrahydrofolate
dihydrolipoylprotein + (6R)-5,10-methylenetetrahydrofolate + NH3
-
requires tetrahydrofolate
-
-
?
S-aminomethyldihydrolipoylprotein + (6S)-tetrahydrofolate
dihydrolipoylprotein + (6R)-5,10-methylenetetrahydrofolate + NH3
-
part of the glycine cleavage system
-
-
?
S-aminomethyldihydrolipoylprotein + (6S)-tetrahydrofolate
dihydrolipoylprotein + (6R)-5,10-methylenetetrahydrofolate + NH3
-
important enzyme in glycine metabolism
-
-
?
S-aminomethyldihydrolipoylprotein + (6S)-tetrahydrofolate
dihydrolipoylprotein + (6R)-5,10-methylenetetrahydrofolate + NH3
-
T-protein catalyzes the tetrahydrofolate-dependent step of the glycine cleavage reaction
-
?
S-aminomethyldihydrolipoylprotein + (6S)-tetrahydrofolate
dihydrolipoylprotein + (6R)-5,10-methylenetetrahydrofolate + NH3
-
tetrahydrofolate-dependent enzyme
-
?
S-aminomethyldihydrolipoylprotein + (6S)-tetrahydrofolate
dihydrolipoylprotein + (6R)-5,10-methylenetetrahydrofolate + NH3
-
part of the glycine cleavage system
-
-
?
S-aminomethyldihydrolipoylprotein + (6S)-tetrahydrofolate
dihydrolipoylprotein + (6R)-5,10-methylenetetrahydrofolate + NH3
-
decarboxylated glycine moiety attached to H-protein + tetrahydrofolate as substrates
-
r
S-aminomethyldihydrolipoylprotein + (6S)-tetrahydrofolate
dihydrolipoylprotein + (6R)-5,10-methylenetetrahydrofolate + NH3
-
T-protein participates in the formation of the one carbon unit and ammonia or the reverse reaction
-
r
S-aminomethyldihydrolipoylprotein + (6S)-tetrahydrofolate
dihydrolipoylprotein + (6R)-5,10-methylenetetrahydrofolate + NH3
-
glycine metabolism
-
-
?
additional information
?
-
-
enzyme is a component of the glycine cleavage system which is composed of P-, H-, L- and T-protein, multienzyme complex
-
-
-
additional information
?
-
-
component of the glycine cleavage system, T-protein is associated with H-protein forming a complex which is composed of one molecule of each of them
-
-
-
additional information
?
-
-
enzyme is a component of the glycine cleavage system which is composed of P-, H-, L- and T-protein, multienzyme complex
-
-
-
additional information
?
-
-
enzyme is a component of the glycine cleavage system which is composed of P-, H-, L- and T-protein, multienzyme complex
-
-
-
additional information
?
-
-
enzyme is a component of the glycine cleavage system which is composed of P-, H-, L- and T-protein, multienzyme complex
-
-
-
additional information
?
-
-
enzyme is a component of the glycine cleavage system which is composed of P-, H-, L- and T-protein, multienzyme complex
-
-
-
additional information
?
-
-
enzyme is a component of the reversible glycine cleavage system which is composed of 4 protein components named as P-, H-, L- and T-protein
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
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
S-aminomethyldihydrolipoylprotein + (6S)-tetrahydrofolate
dihydrolipoylprotein + (6R)-5,10-methylenetetrahydrofolate + NH3
[protein]-S8-aminomethyldihydrolipoyllysine + tetrahydrofolate
[protein]-dihydrolipoyllysine + 5,10-methylenetetrahydrofolate + NH3
-
-
-
-
r
S-aminomethyldihydrolipoylprotein + (6S)-tetrahydrofolate
dihydrolipoylprotein + (6R)-5,10-methylenetetrahydrofolate + NH3
-
part of the glycine cleavage system
-
-
?
S-aminomethyldihydrolipoylprotein + (6S)-tetrahydrofolate
dihydrolipoylprotein + (6R)-5,10-methylenetetrahydrofolate + NH3
-
-
-
-
?
S-aminomethyldihydrolipoylprotein + (6S)-tetrahydrofolate
dihydrolipoylprotein + (6R)-5,10-methylenetetrahydrofolate + NH3
-
part of the glycine cleavage system
-
-
?
S-aminomethyldihydrolipoylprotein + (6S)-tetrahydrofolate
dihydrolipoylprotein + (6R)-5,10-methylenetetrahydrofolate + NH3
-
important enzyme in glycine metabolism
-
-
?
S-aminomethyldihydrolipoylprotein + (6S)-tetrahydrofolate
dihydrolipoylprotein + (6R)-5,10-methylenetetrahydrofolate + NH3
-
part of the glycine cleavage system
-
-
?
S-aminomethyldihydrolipoylprotein + (6S)-tetrahydrofolate
dihydrolipoylprotein + (6R)-5,10-methylenetetrahydrofolate + NH3
-
glycine metabolism
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.151
5,10-methylenetetrahydrofolate
-
N-terminal deletion mutant, His-tagged
0.0092
5,10-methylenetetrahydropteroyltetraglutamate
-
wild-type with His-tag
0.0108
5,10-methylenetetrahydropteroyltetraglutamate
-
mutant L6A, His-tagged
0.0174
5,10-methylenetetrahydropteroyltetraglutamate
-
mutant T4A, His-tagged
0.0382
5,10-methylenetetrahydropteroyltetraglutamate
-
N-terminal deletion mutant, His-tagged
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
9.5
5,10-methylenetetrahydropteroyltetraglutamate
Escherichia coli
-
N-terminal deletion mutant, His-tagged
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
PDB
SCOP
CATH
ORGANISM
UNIPROT
Bartonella henselae (strain ATCC 49882 / DSM 28221 / Houston 1)
Pyrococcus horikoshii (strain ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
monomer
additional information
dimer
-
crystallization data, cloverleaf-like orientation of protomer around a central hole
dimer
-
2 * 46170, calculated; crystallization data, cloverleaf-like orientation of protomer around a central hole
-
additional information
-
construction of low-resolution model and tertiary structure model
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
aminomethyltransferase/T-protein in complex with dihydrolipoate-bearing H-protein and 5-methyltetrahydrofolate, a complex mimicking the ternary complex in the reverse reaction, purified recombinant wild-type and mutant T-proteins, hanging drop vapor diffusion method, mixing of 22-25 mg/ml proteins, T-protein and H protein, with an equal volume of reservoir solution containing 0.095 M 2-[4-(2-hydroxyethyl)-1-piperazinyl]ethanesulfonic acid, pH 7.5, 0.19 M calcium chloride, 26.6% v/v PEG 400, and 5% v/v glycerol, at 15°C, 4-5 days to 2 weeks, soaking of the native crystals in mother liquid containing 1 mM (6S)-5-methyltetrahydrofolate at 15°C for 4 h, X-ray diffraction structure determination and analysis at 2.0 A resolution, molecular replacement
-
apoform, tetrahydrofolate complex, folinic acid complex and lipoic acid complex of enzyme, homology model of human enzyme
-
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C, 20 mM Tris-HCl buffer, pH 8.0, 10 mM 2-mercaptoethanol, 50% v/v glycerol, at least 2 months, stable
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
purification of recombinant enzyme, expressed in Escherichia coli BL21 (DE3)pLysS, and of mutants
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Amt gene is located on chromosome 3p21 and contains 9 exons spanning about 6 kb of genomic sequence
-
C-terminally His6-tagged T-protein wild-type and mutant enzymes expression in Escherichia coli strain BL21(DE3)pLysS
-
cloning and sequencing of the Amt gene with 9 closely spaced exons that are contained within about 5 kb of genomic DNA, encoding a protein of 403 amino acids, cis-acting promoter is likely to be very short, Amt gene may be localized on chromosome 9F
-
gene AMT, genotyping in 14 glycine encephalopathy patients from 13 families from Malaysia, six patients (43%) have biallelic mutations in the AMT gene
-
transfection to Leishmania infantum and Leishmania major
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
decrease of expression of isogene 1 of T-protein component of glcycine cleavage complex in amastigote growth
response to heat stress in higher expression of isogene 1 of T-protein component of glcycine cleavage complex, inducible expression upon excess glycine
decrease of expression of isogene 1 of T-protein component of glcycine cleavage complex in amastigote growth
-
decrease of expression of isogene 1 of T-protein component of glcycine cleavage complex in amastigote growth
-
response to heat stress in higher expression of isogene 1 of T-protein component of glcycine cleavage complex, inducible expression upon excess glycine
-
response to heat stress in higher expression of isogene 1 of T-protein component of glcycine cleavage complex, inducible expression upon excess glycine
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D96N
-
site-directed mutagenesis, both the glycine cleavage and synthesis activities are reduced to 34% compared to the wild-type enzyme
D96N/Y188F
-
site-directed mutagenesis, the mutations abolish both the glycine cleavage and synthesis activities
D97N
-
site-directed mutagenesis, the mutation abolishes both the glycine cleavage and synthesis activities
D97N/Y188F
-
site-directed mutagenesis, the mutations abolish both the glycine cleavage and synthesis activities
K75E
-
mutant with 2.5fold increased Km-value for 5,10-methylenetetrahydrofolate and 8fold increased Km-value for 5,10-methylenetetrahydropteroyltetraglutamate
K81E
-
mutant with 3fold increased Km-value for 5,10-methylenetetrahydrofolate and 16fold increased Km-value for 5,10-methylenetetrahydropteroyltetraglutamate
L6A
-
in contrast to wild-type, quite susceptible to trypsinolysis, 4fold increase in Km-value for reduced H-protein
N113A
-
site-directed mutagenesis, the mutation abolishes both the glycine cleavage and synthesis activities
N113A/R223A
-
site-directed mutagenesis, the mutations abolish both the glycine cleavage and synthesis activities
N113D
-
site-directed mutagenesis, the mutation abolishes both the glycine cleavage and synthesis activities
R223A
-
site-directed mutagenesis, the mutation abolishes both the glycine cleavage and synthesis activities
R223K
-
site-directed mutagenesis, the mutation abolishes both the glycine cleavage and synthesis activities
Y188F
-
site-directed mutagenesis, both the glycine cleavage and synthesis activities are reduced to 83% compared to the wild-type enzyme
E211K
-
polymorphism occurring in patients with glycine encephalopathy, NKH, method for PCR-restriction enzyme analysis
H42R
-
present in many nonketotic hyperglycinemia affected members of an extended Israeli-Arab kindred
N145I
-
nonketotic hyperglycinemia, substitution of conserved N, patient has servere neonatal presentation and died in the newborn period
R265H
-
naturally occurring mutation in glycine encephalopathy patients and the Penan sub-population. Detection of four missense mutations (c.664C4T, c.688G4C, c.794G4A, c.826G4C) and one heterozygous deletion causing frameshift mutation (c.982delG) in AMT gene
R296H
-
mutation occurring in patients with glycine encephalopathy, NKH, method for PCR-restriction enzyme analysis
R318R
-
polymorphism occurring in patients with glycine encephalopathy, NKH, method for PCR-restriction enzyme analysis
R320H
-
allele frequency of 7% for R320H of T-protein in 50 patients with enzymatic confirmation of their diagnostics of nonketotic hyperglycinemia
additional information
additional information
-
N-terminal deletion of 7 amino acids, in contrast to wild-type, quite susceptible to trypsinolysis
additional information
-
allele frequency of 3% for T-protein splice site mutation IVS7-1G-A in 50 patients with enzymatic confirmation of their diagnostics of nonketotic hyperglycinemia, mutation with a one-base deletion 183delC
additional information
-
a subset of nonketotic hyperglycinemia cases is due to mutations in the gene for the T-protein
additional information
-
in 14 glycine encephalopathy patients from 13 families, six patients (43%) have biallelic mutations in the AMT gene, most of which are missense mutations and family-specific
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
-
strategy for molecular investigation of patients with nonketotic hyperglycinemia: defective glycine cleavage enzyme system, composed of P-, H-, T- and L-protein, 15% of patients have a T-protein defect
medicine
-
a subset of nonketotic hyperglycinemia cases is due to mutations in the gene for the T-protein
medicine
-
identification of several mutations and polymorphisms occurring in patients with glycine encephalopathy, NKH, and methods for their PCR-restriction enzyme analysis
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