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Literature summary for 2.1.2.2 extracted from

  • Connelly, S.; DeMartino, J.K.; Boger, D.L.; Wilson, I.A.
    Biological and structural evaluation of 10R- and 10S-methylthio-DDACTHF reveals a new role for sulfur in inhibition of glycinamide ribonucleotide transformylase (2013), Biochemistry, 52, 5133-5144.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

Cloned (Comment) Organism
gene purN, recombinant expression of C-terminally His-tagged enzyme in Escherichia coli strain BL21(DE3) Homo sapiens

Crystallization (Commentary)

Crystallization (Comment) Organism
purified recombinant enzyme in apoform or in complex with inhibitors 10S methylthio-DDACTHF and 10R methylthio-DDACTHF, mixing of 0.002 ml of 15 mg/mL in 20 mM Tris, pH 8.0, 200 mM NaCl, 5 mM DTT, and inhibitors in a 5fold molar excess for complex crystals, with 0.002 ml of reservoir solution containing 0.1 M phosphate/citrate buffer, 1.5-2.0 M ammonium sulfate at pH 4.2, X-ray diffraction structure determination and analysis at 1.52-1.70 A resolution, molecular replacement Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
10-formyl-5,10-dideaza-5,6,7,8-tetrahydrofolic acid
-
Homo sapiens
lometrexol i.e. (6R)-5,10-dideaza-5,6,7,8-tetrahydrofolic acid Homo sapiens
additional information inhibitor design and evalutaion of cofactor analogues, C10 substitution and stereochemistry, pteridine-binding pocket structure and ligand binding, modeling, overview Homo sapiens
N-[(5-[2-[(6R)-2-amino-4-oxo-3,4,5,6,7,8-hexahydropyrido[2,3-d]pyrimidin-6-yl]ethyl]-4-methylthiophen-2-yl)carbonyl]glutamic acid modeling Homo sapiens
N-[(5-[2-[(6R)-2-amino-4-oxo-3,4,5,6,7,8-hexahydropyrido[2,3-d]pyrimidin-6-yl]ethyl]thiophen-2-yl)carbonyl]glutamic acid modeling Homo sapiens
N-[(5-[2-[(6S)-2-amino-4-oxo-4,6,7,8-tetrahydro-3H-pyrimido[5,4-b][1,4]thiazin-6-yl]ethyl]thiophen-2-yl)carbonyl]glutamic acid modeling Homo sapiens
N-[4-[(1R)-4-(2,4-diamino-6-oxo-1,6-dihydropyrimidin-5-yl)-1-(methylsulfanyl)butyl]benzoyl]glutamic acid binding structure analysis, modeling, overview Homo sapiens
N-[4-[(1S)-4-(2,4-diamino-6-oxo-1,6-dihydropyrimidin-5-yl)-1-(methylsulfanyl)butyl]benzoyl]glutamic acid binding structure analysis, modeling, overview Homo sapiens
N-[4-[4-(2,4-diamino-6-oxo-1,6-dihydropyrimidin-5-yl)-1-(methylsulfanyl)butyl]benzoyl]glutamic acid
-
Homo sapiens
N-[4-[6-(2,4-diamino-6-oxo-1,6-dihydropyrimidin-5-yl)-1,1,1-trifluoro-2-oxohexan-3-yl]benzoyl]glutamic acid
-
Homo sapiens
permetrexed
-
Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens P22102
-
-

Purification (Commentary)

Purification (Comment) Organism
recombinant C-terminally His-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography and gel filtration Homo sapiens

Source Tissue

Source Tissue Comment Organism Textmining
leukemia cell
-
Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
10-formyltetrahydrofolate + N1-(5-phospho-D-ribosyl)glycinamide
-
Homo sapiens tetrahydrofolate + N2-formyl-N1-(5-phospho-D-ribosyl)glycinamide
-
?

Synonyms

Synonyms Comment Organism
GAR TFase
-
Homo sapiens
glycinamide ribonucleotide transformylase
-
Homo sapiens

Cofactor

Cofactor Comment Organism Structure
10-formyltetrahydrofolate binding structure and formyl transfer structure and mechanism analysis, overview Homo sapiens

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.000005 0.00005 N-[(5-[2-[(6S)-2-amino-4-oxo-4,6,7,8-tetrahydro-3H-pyrimido[5,4-b][1,4]thiazin-6-yl]ethyl]thiophen-2-yl)carbonyl]glutamic acid pH and temperature not specified in the publication Homo sapiens
0.000005 0.00005 N-[(5-[2-[(6R)-2-amino-4-oxo-3,4,5,6,7,8-hexahydropyrido[2,3-d]pyrimidin-6-yl]ethyl]thiophen-2-yl)carbonyl]glutamic acid pH and temperature not specified in the publication Homo sapiens
0.000005 0.00005 N-[(5-[2-[(6R)-2-amino-4-oxo-3,4,5,6,7,8-hexahydropyrido[2,3-d]pyrimidin-6-yl]ethyl]-4-methylthiophen-2-yl)carbonyl]glutamic acid pH and temperature not specified in the publication Homo sapiens
0.00018
-
N-[4-[(1S)-4-(2,4-diamino-6-oxo-1,6-dihydropyrimidin-5-yl)-1-(methylsulfanyl)butyl]benzoyl]glutamic acid pH and temperature not specified in the publication Homo sapiens
0.00021
-
N-[4-[(1R)-4-(2,4-diamino-6-oxo-1,6-dihydropyrimidin-5-yl)-1-(methylsulfanyl)butyl]benzoyl]glutamic acid pH and temperature not specified in the publication Homo sapiens

General Information

General Information Comment Organism
additional information the enzyme comprises residues 808-1010 for the hGAR Tfase domain (purN) from the native human trifunctional enzyme (purD-purM-purN) Homo sapiens