2.1.2.1: glycine hydroxymethyltransferase
This is an abbreviated version!
For detailed information about glycine hydroxymethyltransferase, go to the full flat file.
Word Map on EC 2.1.2.1
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2.1.2.1
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one-carbon
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pyridoxal
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thymidylate
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purine
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5'-phosphate
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homocysteine
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dihydrofolate
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folate-dependent
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photorespiratory
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photorespiration
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folate-mediated
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pyridoxal-5'-phosphate
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thf
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dtmp
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mthfd1
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plp-dependent
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remethylation
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aldimine
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phgdh
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medicine
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folate-metabolizing
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5,10-methenyltetrahydrofolate
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5'-phosphate-dependent
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antifolate
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hydroxypyruvate
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quinonoid
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5-methyltetrahydrofolate
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glycerate
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5-formyltetrahydrofolate
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drug development
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folate-related
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d-alanine
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c1-tetrahydrofolate
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1-carbon
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5-formyl
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polyglutamate
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l-threonine
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alpha-protons
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slc19a1
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retro-aldol
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degradation
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analysis
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synthesis
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biotechnology
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pharmacology
- 2.1.2.1
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one-carbon
- pyridoxal
- thymidylate
- purine
- 5'-phosphate
- homocysteine
- dihydrofolate
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folate-dependent
-
photorespiratory
-
photorespiration
-
folate-mediated
- pyridoxal-5'-phosphate
- thf
- dtmp
- mthfd1
-
plp-dependent
-
remethylation
-
aldimine
- phgdh
- medicine
-
folate-metabolizing
- 5,10-methenyltetrahydrofolate
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5'-phosphate-dependent
- antifolate
- hydroxypyruvate
-
quinonoid
- 5-methyltetrahydrofolate
- glycerate
- 5-formyltetrahydrofolate
- drug development
-
folate-related
- d-alanine
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c1-tetrahydrofolate
-
1-carbon
-
5-formyl
- polyglutamate
- l-threonine
-
alpha-protons
-
slc19a1
-
retro-aldol
- degradation
- analysis
- synthesis
- biotechnology
- pharmacology
Reaction
Synonyms
AtSHMT3, bsSHMT, bstSHMT, EC 4.1.2.6, eSHMT, GlyA, GlyA protein, glycine hydroxymethyltransferrase, hSHMT, L-serine hydroxymethyltransferase, mitochondrial serine hydroxymethyltransferase, MJ1597, PvSHMT, Rhg4, serine hydroxymethyl transferase, serine hydroxymethylase hydroxymethyltransferase, serine, serine hydroxymethyltransferase, serine hydroxymethyltransferase 1, serine hydroxymethyltransferase 2, serine hydroxymethyltransferase 2alpha, serine transhydroxymethylase, serine:H4F hydroxymethyltransferase, serine:tetrahydrofolate hydroxymethyltransferase, SHM1, SHM2, SHMT, SHMT-1, SHMT-L, SHMT-S, SHMT08, SHMT1, SHMT2, SHMT2alpha, SHMT3, zcSHMT, zebrafish cytosolic serine hydroxymethyltransferase, zebrafish mitochondiral serine hydroxymethyltransferase, zmSHMT
ECTree
2.1.2.1 glycine hydroxymethyltransferaseAdvanced search results
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results (Engineering
Engineering on EC 2.1.2.1 - glycine hydroxymethyltransferase
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PROTEIN VARIANTS 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
L276A
L785A/L276A
the mutation has the effect of lowering the cooperativity of urea denaturation process
L85A
L85A/L276A
P214A
-
the turnover-number is 1.5fold lower than the wild-type value, the Km-value for Ser is 2.1fold lower than the wild-type value, The Km-value for tetrahydropteroylglutamate is 1.3fold higher than the wild-type value, Tm-value in absence of Ser is 3.5°C lower than the wild-type Tm-value. The Tm-value in presence of Ser is 4°C higher than the wild-type value
P214G
-
the turnover-number is 1.5fold lower than the wild-type value, the Km-value for Ser is 1.3fold lower than the wild-type value, The Km-value for tetrahydropteroylglutamate is 1.3fold higher than the wild-type value
P216A
-
the turnover-number is 1.5fold lower than the wild-type value, the Km-value for Ser is 1.2fold lower than the wild-type value. The Km-value for tetrahydropteroylglutamate is 1.3fold higher than the wild-type value, Tm-value in absence of Ser is 3.5°C higher than the wild-type Tm-value, The Tm-value in presence of Ser is 0.5°C higher than the wild-type value
P216G
-
the turnover-number is 8.3fold lower than the wild-type value, the Km-value for Ser is 1.9fold higher than the wild-type value. The Km-value for tetrahydropteroylglutamate is 5.7fold higher than the wild-type value
P218A
-
the turnover-number is 1.1fold lower than the wild-type value, the Km-value for Ser is 2.3fold lower than the wild-type value. The Km-value for tetrahydropteroylglutamate is 1.3fold higher than the wild-type value, double thermal transition that is considerably lower than wild-type enzyme, no increase in thermal stability upon binding serine
P218G
-
the turnover-number is 1.5fold lower than the wild-type value, the Km-value for Ser is 2.3fold lower than the wild-type value. The Km-value for tetrahydropteroylglutamate is 1.1fold higher than the wild-type value
P258A
-
the turnover-number is below 0.5 per min, the KM-value for Ser is 26.7fold higher than the wild-type value
P264A
-
the turnover-number is 3fold lower than the wild-type value, the Km-value for Ser is 1.1fold higher than the wild-type value, The Km-value for tetrahydropteroylglutamate is 1.1fold higher than the wild-type value, Tm-value in absence of Ser is 9°C lower than the wild-type Tm-value. The Tm-value in presence of Ser is 11.5°C lower than the wild-type value
P264G
-
the turnover-number is 42.9fold lower than the wild-type value, the Km-value for Ser is 4.4fold higher than the wild-type value
E53Q
-
site-directed mutagenesis, mutation of a substrate binding residue, the mutant retains tetrahydrofolate-independent aldolase activity
F351G
the mutation has no effect on tetrahydrofolate-independent and tetrahydrofolate-dependent activities
K226M
-
mutant enzymes is inactive, drastic rate of formation of the quinoid intermediate. It contains 1 mol of pyridoxal 5'-phosphate per mol of subunit. pyridoxal 5'-phosphate is bound at the active site in an orientation different from that of the wild-type enzyme. K-226 is responsible for flipping of pyridoxal 5'-phosphate from one orientation to another which is crucial for tetrahydropteroylglutamate-dependent Calpha-Cbeta bond cleavage of L-Ser
K226Q
-
mutant enzymes is inactive, drastic rate of formation of the quinoid intermediate. It contains 1 mol of pyridoxal 5'-phosphate oer mol of subunit. pyridoxal 5'-phosphate is bound at the active site in an orientation different from that of the wild-type enzyme. K-226 is responsible for flipping of pyridoxal 5'-phosphate from one orientation to another which is crucial for tetrahydropteroylglutamate-dependent Calpha-Cbeta bond cleavage of L-Ser
N341A
the mutant is inactive for the tetrahydrofolate-dependent activity, while the mutation has no effect on tetrahydrofolate-independent activity
Y51F
-
the mutation results in a complete loss of tetrahydrofolate-dependent and tetrahydrofolate-independent activities
Y60A
the mutant is inactive for the tetrahydrofolate-dependent activity, while the mutation has no effect on tetrahydrofolate-independent activity
Y61A
Y61F
-
site-directed mutagenesis, the bsSHMT mutant has lost aldolase activity to L-allo-threonine
I249L
the catalytic efficiency of the mutant is 2.78fold higher than that of the wild type enzyme
A206C
the mutation yields an enzyme that forms a 3-bromopyruvate-enzyme complex and is completely inactivated
H135N/R137A/E168N
tetrameric active mutant with a modified, less stable, tetrameric interface
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, 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
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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, 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
G132P
-
the mutant shows 301% activity compared to the wild type enzyme
H61G/G132P
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the mutant shows 356% activity compared to the wild type enzyme
E75L
E75Q
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
E74K
-
specific activities drastically reduced with serine as substrate, but D-alanine transamination and allothreonine cleavage at rates comparable with wild-type enzyme
E74Q
H147N
-
site-directed mutagenesis, mutation of a substrate binding residue, the mutant retains tetrahydrofolate-independent aldolase activity
R262A
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KM-value for L-Ser is 5.2fold higher than the wild-type value, the turnover-number is 5.25fold lower than the wild-type value, no transamination reaction with D-Ala, reaction with L-allo-Thr is 20fold decreased compared to wild-type value. L-Ser is unable to enhance the thermal stability as it does in wild-type enzyme
S52A
-
KM-value for L-Ser is 1.3fold higher than the wild-type value, the turnover-number is 6fold lower than the wild-type value, transamination reaction with D-Ala is 20% of the wild-type activity, reaction with L-allo-Thr is 15% of the wild-type activity. L-Ser is unable to enhance the thermal stability as it does in wild-type enzyme
S52C
-
KM-value for L-Ser is 11.2fold higher than the wild-type value, the turnover-number is 21fold lower than the wild-type value, no transamination reaction with D-Ala, no reaction with L-allo-Thr. L-Ser is unable to enhance the thermal stability as it does in wild-type enzyme
Y82F
-
95% loss of activity, kcat and Km decreased, a role in stabilizing the quinonoid intermediate
Y55T
K251Q
-
oligomeric structure not affected, but inactive in both the presence and absence of pyridoxal phosphate
K251R
-
oligomeric structure not affected, catalytic activity in the presence of pyridoxal phosphate also unaffected
additional information
L276A
the mutant is in the monomeric state and shows reduced activity
L276A
the mutation has the effect of lowering the cooperativity of urea denaturation process
L276A
-
site-directed mutagenesis, mutation in the third hydrophobic cluster. The decrease of hydrophobic contact area in the mutant causes a shift of the equilibrium between dimeric and monomeric forms in favor of the latter, pyridoxal 5'-phosphate binding stabilizes the dimeric form of the mutant
L85A
the apo-L85A mutant enzyme is approximately 75% dimeric and shows reduced activity
L85A
-
site-directed mutagenesis, mutation in the third hydrophobic cluster. The decrease of hydrophobic contact area in the mutant causes a shift of the equilibrium between dimeric and monomeric forms in favor of the latter, pyridoxal 5'-phosphate binding stabilizes the dimeric form of the mutant
L85A/L276A
the mutant is in the monomeric state and shows reduced activity
L85A/L276A
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site-directed mutagenesis, mutation in the third hydrophobic cluster. The decrease of hydrophobic contact area in the mutant causes a shift of the equilibrium between dimeric and monomeric forms in favor of the latter, pyridoxal 5'-phosphate binding stabilizes the dimeric form of the mutant
Y61A
-
the mutation results in a complete loss of tetrahydrofolate-dependent and tetrahydrofolate independent activities
Y61A
-
site-directed mutagenesis, the bsSHMT mutant has lost aldolase activity to L-allo-threonine
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
E75L
-
site-directed mutagenesis, mutation of a substrate binding residue, the mutant retains tetrahydrofolate-independent aldolase activity
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
E75Q
-
site-directed mutagenesis, mutation of a substrate binding residue, the mutant retains tetrahydrofolate-independent aldolase activity
E74Q
-
specific activities drastically reduced with serine as substrate, but D-alanine transamination and allothreonine cleavage at rates comparable with wild type enzyme
E74Q
-
site-directed mutagenesis, mutation of a substrate binding residue, the mutant retains tetrahydrofolate-independent aldolase activity
Y55T
the variant tolerates aromatic and aliphatic aldehydes as well as hydroxy- and nitrogen-containing aldehydes as acceptors
Y55T
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the variant tolerates aromatic and aliphatic aldehydes as well as hydroxy- and nitrogen-containing aldehydes as acceptors
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additional information
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5-CHO-THF cycloligase mutant, doubled leaf 5-formyltetrahydrofolate level, little impact on SHMT activity, but glycine content of mutant leaves is 19fold higher than the wild-type, also a small accumulation of serine in the mutant relative to the wild-type
additional information
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construction of chimeric enzymes by swapping the structural domains between the bsSHMT from Bacillus subtilis and the bstSHMT frok Bacillus stearothermophilus and generation of the two chimeric proteins bsbstc and bstbsc. The chimeras have secondary structure, tyrosine and pyridoxal 5'-phosphate microenvironment similar to that of the wild-type proteins. The chimeras show enzymatic activity slightly higher than that of the wild-type proteins.Unlike the wild-type enzyme bsSHMT, which undergoes dissociation of native dimer into monomers at low guanidinium chloride concentrations, resulting in a non-cooperative unfolding of the enzyme, its chimera bsbstc, having the C-terminal domain of bstSHMT is resistant to low guanidinium chloride concentration and shows a guanidinium-chloride-induced cooperative unfolding from native dimer to unfolded monomer. The wild-type dimeric bstSHMT is resistant to low guanidinium chloride concentrations and shows a guanidinium chloride-induced cooperative unfolding, whereas its chimera bstbsc, having the C-terminal domain of bsSHMT, shows dissociation of native dimer into monomer at low guanidinium chloride concentrations and a guanidinium-induced non-cooperative unfolding
additional information
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generation of a chimera from Bacillus stearothermophilus and Bacillus subtilis SHMTs by domain swapping, quarternary structure analysis, overview
additional information
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SHMT activity controlled by Ptac, greatly reduced SHMT activity if no isopropyl-thio-beta-D-galactopyranoside is present, is explicitly prone to chromosomal mutations and rearrangements, thus making the strain unsuitable for large-scale fermentations
additional information
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mutant strain 1D19 from first round of DNA-shuffling, shows a 1.7fold increase in SHMT activity, mutant strain 2G31 from the second round of shuffling shows a 2.8fold increase in SHMT activity, mutant strain 3E7 from third round of shuffling, approximately 8fold increased enzyme activity and 41fold increased enzyme productivity as compared with its wild-type parent
additional information
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immobilization of cells using 3% alginate (w/v), 5 g cells (wet), and 2% (w/v) CaCl2 solution
additional information
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mutant strain 1D19 from first round of DNA-shuffling, shows a 1.7fold increase in SHMT activity, mutant strain 2G31 from the second round of shuffling shows a 2.8fold increase in SHMT activity, mutant strain 3E7 from third round of shuffling, approximately 8fold increased enzyme activity and 41fold increased enzyme productivity as compared with its wild-type parent
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additional information
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immobilization of cells using 3% alginate (w/v), 5 g cells (wet), and 2% (w/v) CaCl2 solution
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additional information
-
construction of chimeric enzymes by swapping the structural domains between the bsSHMT from Bacillus subtilis and the bstSHMT from Bacillus stearothermophilus and generation of the two chimeric proteins bsbstc and bstbsc. The chimeras have secondary structure, tyrosine and pyridoxal 5'-phosphate microenvironment similar to that of the wild-type proteins. The chimeras show enzymatic activity slightly higher than that of the wild-type proteins.Unlike the wild-type enzyme bsSHMT, which undergoes dissociation of native dimer into monomers at low guanidinium chloride concentrations, resulting in a non-cooperative unfolding of the enzyme, its chimera bsbstc, having the C-terminal domain of bstSHMT is resistant to low guanidinium chloride concentration and shows a guanidinium-chloride-induced cooperative unfolding from native dimer to unfolded monomer. The wild-type dimeric bstSHMT is resistant to low guanidinium chloride concentrations and shows a guanidinium chloride-induced cooperative unfolding, whereas its chimera bstbsc, having the C-terminal domain of bsSHMT, shows dissociation of native dimer into monomer at low guanidinium chloride concentrations and a guanidinium-induced non-cooperative unfolding
additional information
-
generation of a chimera from Bacillus stearothermophilus and Bacillus subtilis SHMTs by domain swapping, quarternary structure analysis, overview
additional information
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mutation of the consensus metal regulatory element sequence decreases the promoter activity of the -219 to -1 fragment by 60% in the absence of L-mimosine and attenuates L-mimosine inhibition by nearly 40%, mutation of the NF1 consensus sequence in the SHMT1 promoter -219 to -1 partially attenuates L-mimosine inhibition by ca. 20% without influencing SHMT1 promoter activity
additional information
sequencing of 12 Plasmodium vivax SHMT isolates reveals limited polymorphisms in 3 noncoding regions
additional information
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sequencing of 12 Plasmodium vivax SHMT isolates reveals limited polymorphisms in 3 noncoding regions
additional information
the SaSHMT has the potential for industrial applications due to its tolerance of alkaline environment and a relatively high enzymatic conversion rate
additional information
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the SaSHMT has the potential for industrial applications due to its tolerance of alkaline environment and a relatively high enzymatic conversion rate
