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Literature summary extracted from

  • Dennis, M.L.; Pitcher, N.P.; Lee, M.D.; DeBono, A.J.; Wang, Z.C.; Harjani, J.R.; Rahmani, R.; Cleary, B.; Peat, T.S.; Baell, J.B.; Swarbrick, J.D.
    Structural basis for the selective binding of inhibitors to 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase from Staphylococcus aureus and Escherichia coli (2016), J. Med. Chem., 59, 5248-5263.
    View publication on PubMed

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.7.6.3 recombinant expression of His6-tagged enzyme in Escherichia coli strain BL21(DE3) Escherichia coli

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
2.7.6.3 purified recombinant detagged enzyme in complex with different inhibitors and AMPCPP, sitting-drop vapor diffusion method, mixing of 2.2 mg/ml protein in 20 mM Tris-HCl buffer, pH 8.0, 100 mM NaCl, with reservoir solution containing 20% w/v PEG 4000, 0.1 M TrisCl, and 0.172 M CaCl2, or 0.1 M HEPES-NaOH, pH 7.5, 0.2 M CaCl2, and 25-30% PEG 4000, 16-20°C, addition of 2 mM MgCl2, 1 mM AMPCPP, and 1 mM of inhibitor, X-ray diffraction structure determination and analysis, molecular replacement Escherichia coli
2.7.6.3 purified recombinant enzyme in complex with AMPCPP and different inhibitors, sitting-drop vapor diffusion method, mixing of 6.9 mg/ml protein in in 20 mM Tris-HCl buffer, pH 8.0, 100 mM NaCl, with reservoir solution containing 0.186 M sodium nitrate, 18.4% w/v PEG 3000, 2 mM MgCl2, 1 mM AMPCPP, and 1 mM inhibitor or 0.1 M Tris-HCl, pH 8.5, 0.2 M MgCl2, 20% PEG 8000, 0.05 M sodium thiocyanate, 1 mM AMPCPP, and 1 mM inhibitor, X-ray diffraction structure determination and analysis, molecular replacement Staphylococcus aureus

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.7.6.3 2-(((2-amino-6-oxo-6,9-dihydro-1H-purin-8-yl)thio)methyl)-5-fluorobenzonitrile
-
 Escherichia coli
2.7.6.3 2-(((2-amino-6-oxo-6,9-dihydro-1H-purin-8-yl)thio)methyl)-5-fluorobenzonitrile
-
 Staphylococcus aureus
2.7.6.3 2-(((2-amino-6-oxo-6,9-dihydro-1H-purin-8-yl)thio)methyl)-benzonitrile
-
 Escherichia coli
2.7.6.3 2-(((2-amino-6-oxo-6,9-dihydro-1H-purin-8-yl)thio)methyl)-benzonitrile
-
 Staphylococcus aureus
2.7.6.3 2-((2-amino-6-oxo-6,9-dihydro-1H-purin-8-yl)thio)-N,N-diethylacetamide
-
 Escherichia coli
2.7.6.3 2-((2-amino-6-oxo-6,9-dihydro-1H-purin-8-yl)thio)-N,N-diethylacetamide
-
 Staphylococcus aureus
2.7.6.3 2-((2-amino-6-oxo-6,9-dihydro-1H-purin-8-yl)thio)-N,N-dimethylacetamide
-
 Escherichia coli
2.7.6.3 2-((2-amino-6-oxo-6,9-dihydro-1H-purin-8-yl)thio)-N,N-dimethylacetamide
-
 Staphylococcus aureus
2.7.6.3 2-((2-amino-6-oxo-6,9-dihydro-1H-purin-8-yl)thio)-N-ethyl-N-methylpropanamide
-
 Escherichia coli
2.7.6.3 2-((2-amino-6-oxo-6,9-dihydro-1H-purin-8-yl)thio)-N-ethyl-N-methylpropanamide
-
 Staphylococcus aureus
2.7.6.3 2-((2-amino-6-oxo-6,9-dihydro-1H-purin-8-yl)thio)-N-isobutylacetamide
-
 Escherichia coli
2.7.6.3 2-((2-amino-6-oxo-6,9-dihydro-1H-purin-8-yl)thio)-N-isobutylacetamide
-
 Staphylococcus aureus
2.7.6.3 2-((2-amino-6-oxo-6,9-dihydro-1H-purin-8-yl)thio)-N-methylacetamide
-
 Escherichia coli
2.7.6.3 2-((2-amino-6-oxo-6,9-dihydro-1H-purin-8-yl)thio)-N-methylacetamide
-
 Staphylococcus aureus
2.7.6.3 2-amino-8-((2,3-dihydroxypropyl)thio)-1,9-dihydro-6Hpurin-6-one
-
 Escherichia coli
2.7.6.3 2-amino-8-((2,3-dihydroxypropyl)thio)-1,9-dihydro-6Hpurin-6-one
-
 Staphylococcus aureus
2.7.6.3 2-amino-8-((2,3-dimethylbenzyl)thio)-1,9-dihydro-6Hpurin-6-one
-
 Escherichia coli
2.7.6.3 2-amino-8-((2,3-dimethylbenzyl)thio)-1,9-dihydro-6Hpurin-6-one
-
 Staphylococcus aureus
2.7.6.3 2-amino-8-((2,4-difluorobenzyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Escherichia coli
2.7.6.3 2-amino-8-((2,4-difluorobenzyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Staphylococcus aureus
2.7.6.3 2-amino-8-((2,5-dimethylbenzyl)thio)-1,9-dihydro-6Hpurin-6-one
-
 Escherichia coli
2.7.6.3 2-amino-8-((2,5-dimethylbenzyl)thio)-1,9-dihydro-6Hpurin-6-one
-
 Staphylococcus aureus
2.7.6.3 2-amino-8-((2,6-difluorobenzyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Escherichia coli
2.7.6.3 2-amino-8-((2,6-difluorobenzyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Staphylococcus aureus
2.7.6.3 2-amino-8-((2-(2-oxopyrrolidin-1-yl)ethyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Escherichia coli
2.7.6.3 2-amino-8-((2-(2-oxopyrrolidin-1-yl)ethyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Staphylococcus aureus
2.7.6.3 2-amino-8-((2-(4-bromophenyl)-2-oxoethyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Escherichia coli
2.7.6.3 2-amino-8-((2-(4-bromophenyl)-2-oxoethyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Staphylococcus aureus
2.7.6.3 2-amino-8-((2-(trifluoromethyl)benzyl)thio)-1,9-dihydro-6Hpurin-6-one
-
 Escherichia coli
2.7.6.3 2-amino-8-((2-(trifluoromethyl)benzyl)thio)-1,9-dihydro-6Hpurin-6-one
-
 Staphylococcus aureus
2.7.6.3 2-amino-8-((2-bromobenzyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Escherichia coli
2.7.6.3 2-amino-8-((2-bromobenzyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Staphylococcus aureus
2.7.6.3 2-amino-8-((2-chlorobenzyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Escherichia coli
2.7.6.3 2-amino-8-((2-chlorobenzyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Staphylococcus aureus
2.7.6.3 2-amino-8-((2-fluoro-3-methylbenzyl)thio)-1,9-dihydro-6Hpurin-6-one
-
 Escherichia coli
2.7.6.3 2-amino-8-((2-fluoro-3-methylbenzyl)thio)-1,9-dihydro-6Hpurin-6-one
-
 Staphylococcus aureus
2.7.6.3 2-amino-8-((2-fluoro-4-methoxybenzyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Escherichia coli
2.7.6.3 2-amino-8-((2-fluoro-4-methoxybenzyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Staphylococcus aureus
2.7.6.3 2-amino-8-((2-fluoro-5-methylbenzyl)thio)-1,9-dihydro-6Hpurin-6-one
-
 Escherichia coli
2.7.6.3 2-amino-8-((2-fluoro-5-methylbenzyl)thio)-1,9-dihydro-6Hpurin-6-one
-
 Staphylococcus aureus
2.7.6.3 2-amino-8-((2-fluorobenzyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Escherichia coli
2.7.6.3 2-amino-8-((2-fluorobenzyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Staphylococcus aureus
2.7.6.3 2-amino-8-((2-hydroxyethyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Escherichia coli
2.7.6.3 2-amino-8-((2-hydroxyethyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Staphylococcus aureus
2.7.6.3 2-amino-8-((2-methoxyethyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Escherichia coli
2.7.6.3 2-amino-8-((2-methoxyethyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Staphylococcus aureus
2.7.6.3 2-amino-8-((2-methylbenzyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Escherichia coli
2.7.6.3 2-amino-8-((2-methylbenzyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Staphylococcus aureus
2.7.6.3 2-amino-8-((2-nitrobenzyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Escherichia coli
2.7.6.3 2-amino-8-((2-nitrobenzyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Staphylococcus aureus
2.7.6.3 2-amino-8-((2-oxo-2-phenylethyl)thio)-1,9-dihydro-6Hpurin-6-one
-
 Escherichia coli
2.7.6.3 2-amino-8-((2-oxo-2-phenylethyl)thio)-1,9-dihydro-6Hpurin-6-one
-
 Staphylococcus aureus
2.7.6.3 2-amino-8-((3,3,3-trifluoro-2-hydroxypropyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Escherichia coli
2.7.6.3 2-amino-8-((3,3,3-trifluoro-2-hydroxypropyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Staphylococcus aureus
2.7.6.3 2-amino-8-((3,4-difluorobenzyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Escherichia coli
2.7.6.3 2-amino-8-((3,4-difluorobenzyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Staphylococcus aureus
2.7.6.3 2-amino-8-((3,5-bis(trifluoromethyl)benzyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Escherichia coli
2.7.6.3 2-amino-8-((3,5-bis(trifluoromethyl)benzyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Staphylococcus aureus
2.7.6.3 2-amino-8-((3,5-dimethylbenzyl)thio)-1,9-dihydro-6Hpurin-6-one
-
 Escherichia coli
2.7.6.3 2-amino-8-((3,5-dimethylbenzyl)thio)-1,9-dihydro-6Hpurin-6-one
-
 Staphylococcus aureus
2.7.6.3 2-amino-8-((3-(trifluoromethoxy)benzyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Escherichia coli
2.7.6.3 2-amino-8-((3-(trifluoromethoxy)benzyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Staphylococcus aureus
2.7.6.3 2-amino-8-((3-bromobenzyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Escherichia coli
2.7.6.3 2-amino-8-((3-bromobenzyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Staphylococcus aureus
2.7.6.3 2-amino-8-((3-chlorobenzyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Escherichia coli
2.7.6.3 2-amino-8-((3-chlorobenzyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Staphylococcus aureus
2.7.6.3 2-amino-8-((3-fluorobenzyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Escherichia coli
2.7.6.3 2-amino-8-((3-fluorobenzyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Staphylococcus aureus
2.7.6.3 2-amino-8-((3-hydroxypropyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Escherichia coli
2.7.6.3 2-amino-8-((3-hydroxypropyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Staphylococcus aureus
2.7.6.3 2-amino-8-((3-methoxybenzyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Escherichia coli
2.7.6.3 2-amino-8-((3-methoxybenzyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Staphylococcus aureus
2.7.6.3 2-amino-8-((3-methylbenzyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Escherichia coli
2.7.6.3 2-amino-8-((3-methylbenzyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Staphylococcus aureus
2.7.6.3 2-amino-8-((3-nitrobenzyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Escherichia coli
2.7.6.3 2-amino-8-((3-nitrobenzyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Staphylococcus aureus
2.7.6.3 2-amino-8-((4-(trifluoromethoxy)benzyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Escherichia coli
2.7.6.3 2-amino-8-((4-(trifluoromethoxy)benzyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Staphylococcus aureus
2.7.6.3 2-amino-8-((4-(trifluoromethyl)benzyl)thio)-1,9-dihydro-6Hpurin-6-one
-
 Escherichia coli
2.7.6.3 2-amino-8-((4-(trifluoromethyl)benzyl)thio)-1,9-dihydro-6Hpurin-6-one
-
 Staphylococcus aureus
2.7.6.3 2-amino-8-((4-bromobenzyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Escherichia coli
2.7.6.3 2-amino-8-((4-bromobenzyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Staphylococcus aureus
2.7.6.3 2-amino-8-((4-chlorobenzyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Escherichia coli
2.7.6.3 2-amino-8-((4-chlorobenzyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Staphylococcus aureus
2.7.6.3 2-amino-8-((4-fluoro-2-methylbenzyl)thio)-1,9-dihydro-6Hpurin-6-one
-
 Escherichia coli
2.7.6.3 2-amino-8-((4-fluoro-2-methylbenzyl)thio)-1,9-dihydro-6Hpurin-6-one
-
 Staphylococcus aureus
2.7.6.3 2-amino-8-((4-fluoro-3-methylbenzyl)thio)-1,9-dihydro-6Hpurin-6-one
-
 Escherichia coli
2.7.6.3 2-amino-8-((4-fluoro-3-methylbenzyl)thio)-1,9-dihydro-6Hpurin-6-one
-
 Staphylococcus aureus
2.7.6.3 2-amino-8-((4-fluorobenzyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Escherichia coli
2.7.6.3 2-amino-8-((4-fluorobenzyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Staphylococcus aureus
2.7.6.3 2-amino-8-((4-methoxybenzyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Escherichia coli
2.7.6.3 2-amino-8-((4-methoxybenzyl)thio)-1,9-dihydro-6H-purin-6-one
-
 Staphylococcus aureus
2.7.6.3 2-amino-8-(benzylthio)-1,9-dihydro-6H-purin-6-one
-
 Escherichia coli
2.7.6.3 2-amino-8-(benzylthio)-1,9-dihydro-6H-purin-6-one
-
 Staphylococcus aureus
2.7.6.3 3-(((2-amino-6-oxo-6,9-dihydro-1H-purin-8-yl)thio)methyl)-benzoic acid
-
 Escherichia coli
2.7.6.3 3-(((2-amino-6-oxo-6,9-dihydro-1H-purin-8-yl)thio)methyl)-benzoic acid
-
 Staphylococcus aureus
2.7.6.3 3-(((2-amino-6-oxo-6,9-dihydro-1H-purin-8-yl)thio)methyl)-benzonitrile
-
 Escherichia coli
2.7.6.3 3-(((2-amino-6-oxo-6,9-dihydro-1H-purin-8-yl)thio)methyl)-benzonitrile
-
 Staphylococcus aureus
2.7.6.3 4-(((2-amino-6-oxo-6,9-dihydro-1H-purin-8-yl)thio)methyl)-3-fluorobenzonitrile
-
 Escherichia coli
2.7.6.3 4-(((2-amino-6-oxo-6,9-dihydro-1H-purin-8-yl)thio)methyl)-3-fluorobenzonitrile
-
 Staphylococcus aureus
2.7.6.3 4-(((2-amino-6-oxo-6,9-dihydro-1H-purin-8-yl)thio)methyl)-benzonitrile
-
 Escherichia coli
2.7.6.3 4-(((2-amino-6-oxo-6,9-dihydro-1H-purin-8-yl)thio)methyl)-benzonitrile
-
 Staphylococcus aureus
2.7.6.3 5-(((2-amino-6-oxo-6,9-dihydro-1H-purin-8-yl)thio)methyl)-2-fluorobenzonitrile
-
 Escherichia coli
2.7.6.3 5-(((2-amino-6-oxo-6,9-dihydro-1H-purin-8-yl)thio)methyl)-2-fluorobenzonitrile
-
 Staphylococcus aureus
2.7.6.3 8-((2-(1,3-dioxan-2-yl)ethyl)thio)-2-amino-1,9-dihydro-6Hpurin-6-one
-
 Escherichia coli
2.7.6.3 8-((2-(1,3-dioxan-2-yl)ethyl)thio)-2-amino-1,9-dihydro-6Hpurin-6-one
-
 Staphylococcus aureus
2.7.6.3 8-((2-([1,1'-biphenyl]-4-yl)-2-oxoethyl)thio)-2-amino-1,9-dihydro-6H-purin-6-one
-
 Escherichia coli
2.7.6.3 8-((2-([1,1'-biphenyl]-4-yl)-2-oxoethyl)thio)-2-amino-1,9-dihydro-6H-purin-6-one
-
 Staphylococcus aureus
2.7.6.3 8-mercaptoguanine
-
 Escherichia coli
2.7.6.3 8-mercaptoguanine
-
 Staphylococcus aureus
2.7.6.3 additional information synthesis of a series of S-functionalized 8-mercaptoguanine analogues as substrate-site inhibitors of enzyme HPPK, binding structure analysis, and comparison of inhibition efficiency with the enzymes from Staphylococcus aureus and Escherichia coli, KD values, overview Escherichia coli
2.7.6.3 additional information synthesis of a series of S-functionalized 8-mercaptoguanine analogues as substrate-site inhibitors of enzyme HPPK, binding structure analysis, and comparison of inhibition efficiency with the enzymes from Staphylococcus aureus and Escherichia coli, KD values, overview Staphylococcus aureus

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
2.7.6.3 Mg2+ required Staphylococcus aureus
2.7.6.3 Mg2+ required Escherichia coli

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.7.6.3 ATP + 2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine Staphylococcus aureus
-
 AMP + (2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate
-
 ?
2.7.6.3 ATP + 2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine Escherichia coli
-
 AMP + (2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
2.7.6.3 Escherichia coli P26281
-
-
2.7.6.3 Staphylococcus aureus
-
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
2.7.6.3 recombinant His6-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography, tag cleavage by TEV protease, and gel filtration Escherichia coli

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.7.6.3 ATP + 2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine
-
 Staphylococcus aureus AMP + (2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate
-
 ?
2.7.6.3 ATP + 2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine
-
 Escherichia coli AMP + (2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate
-
 ?

Synonyms

EC Number Synonyms Comment Organism
2.7.6.3 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase
-
 Staphylococcus aureus
2.7.6.3 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase
-
 Escherichia coli
2.7.6.3 HPPK
-
 Staphylococcus aureus
2.7.6.3 HPPK
-
 Escherichia coli

Cofactor

EC Number Cofactor Comment Organism Structure
2.7.6.3 ATP
-
 Staphylococcus aureus
2.7.6.3 ATP
-
 Escherichia coli

General Information

EC Number General Information Comment Organism
2.7.6.3 metabolism the enzyme is a member of the folate biosynthesis pathway Staphylococcus aureus
2.7.6.3 metabolism the enzyme is a member of the folate biosynthesis pathway Escherichia coli