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Literature summary extracted from

  • Eng, W.; Hockova, D.; Spacek, P.; Baszczynski, O.; Janeba, Z.; Naesens, L.; Keough, D.; Guddat, L.
    Crystal structures of acyclic nucleoside phosphonates in complex with Escherichia coli hypoxanthine phosphoribosyltransferase (2016), ChemistrySelect, 1, 6267-6276 .
No PubMed abstract available

Application

EC Number Application Comment Organism
2.4.2.8 pharmacology inhibitors of EcHPRT may fill a specific niche for the treatment of uropathogenic Escherichia coli infections Escherichia coli

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
2.4.2.8 enzyme in complex with inhibitors (2-[(2,3-dihydroxypropyl)[2-(6-oxo-1,6-dihydro-9H-purin-9-yl)ethyl]amino]ethyl)phosphonic acid, 9-[(N-phosphonoethyl-N-phosphonomethyl)-2-aminoethyl]-hypoxanthine, 9-[(N-phosphonoethyl-N-phosphonoethoxyethyl)-2-aminoethyl]-hypoxanthine, (2-[[2-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)ethyl][2-(2-phosphonoethoxy)ethyl]amino]ethyl)phosphonic acid, [[2-[(6-oxo-1,6-dihydro-9H-purin-9-yl)methyl]propane-1,3-diyl]bis(oxymethylene)]bis(phosphonic acid), and [[[(4-oxo-4,5-dihydro-3H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]azanediyl]di(propane-3,1-diyl)]bis(phosphonic acid), X-ray diffraction structure determination and analysis at 2.55-2.9 A resolution Escherichia coli

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.4.2.8 (2-[(2,3-dihydroxypropyl)[2-(6-oxo-1,6-dihydro-9H-purin-9-yl)ethyl]amino]ethyl)phosphonic acid
-
 Escherichia coli
2.4.2.8 (2-[[2-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)ethyl][2-(2-phosphonoethoxy)ethyl]amino]ethyl)phosphonic acid
-
 Escherichia coli
2.4.2.8 2-((2,3-dihydroxypropyl)(2-(hypoxanthin-9-yl)ethyl)-amino)ethyl phosphonate weak inhibition Escherichia coli
2.4.2.8 9-[(N-phosphonoethyl-N-phosphonobutyl)-2-aminoethyl]hypoxanthine
-
 Escherichia coli
2.4.2.8 9-[(N-phosphonoethyl-N-phosphonoethoxyethyl)-2-aminoethyl]-hypoxanthine
-
 Escherichia coli
2.4.2.8 9-[(N-phosphonoethyl-N-phosphonomethoxyethyl)-2-aminoethyl]hypoxanthine
-
 Escherichia coli
2.4.2.8 9-[(N-phosphonoethyl-N-phosphonomethyl)-2-aminoethyl]-hypoxanthine
-
 Escherichia coli
2.4.2.8 GMP competitive inhibitor Escherichia coli
2.4.2.8 IMP competitive inhibitor Escherichia coli
2.4.2.8 monophosphonate-2-(phosphonoethoxy)ethyl hypoxanthine PEEHx Escherichia coli
2.4.2.8 additional information EcHPRT inhibitor design, synthesis and optimization. Several acyclic nucleoside phosphonates (ANPs) have previously been identified as inhibitors of EcXGPRT and EcHPRT, and the most potent of these have Ki values as low as 10 nM for EcXGPRT and 0.8 mM for EcHPRT. Inhibitors binding structures, detailed overview Escherichia coli
2.4.2.8 [[2-[(6-oxo-1,6-dihydro-9H-purin-9-yl)methyl]propane-1,3-diyl]bis(oxymethylene)]bis(phosphonic acid)
-
 Escherichia coli
2.4.2.8 [[[(4-oxo-4,5-dihydro-3H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]azanediyl]di(propane-3,1-diyl)]bis(phosphonic acid)
-
 Escherichia coli
2.4.2.22 (2-[(2,3-dihydroxypropyl)[2-(6-oxo-1,6-dihydro-9H-purin-9-yl)ethyl]amino]ethyl)phosphonic acid
-
 Escherichia coli
2.4.2.22 (2-[[2-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)ethyl][2-(2-phosphonoethoxy)ethyl]amino]ethyl)phosphonic acid
-
 Escherichia coli
2.4.2.22 9-[(N-phosphonoethyl-N-phosphonobutyl)-2-aminoethyl]hypoxanthine
-
 Escherichia coli
2.4.2.22 9-[(N-phosphonoethyl-N-phosphonoethoxyethyl)-2-aminoethyl]-hypoxanthine
-
 Escherichia coli
2.4.2.22 9-[(N-phosphonoethyl-N-phosphonomethoxyethyl)-2-aminoethyl]hypoxanthine
-
 Escherichia coli
2.4.2.22 9-[(N-phosphonoethyl-N-phosphonomethyl)-2-aminoethyl]-hypoxanthine
-
 Escherichia coli
2.4.2.22 additional information EcXGPRT inhibitor design, synthesis and optimization. Several acyclic nucleoside phosphonates (ANPs) have previously been identified as inhibitors of EcXGPRT and EcHPRT and the most potent of these have Ki values as low as 10 nM for EcXGPRT and 0.8 mM for EcHPRT Escherichia coli
2.4.2.22 [[2-[(6-oxo-1,6-dihydro-9H-purin-9-yl)methyl]propane-1,3-diyl]bis(oxymethylene)]bis(phosphonic acid)
-
 Escherichia coli
2.4.2.22 [[[(4-oxo-4,5-dihydro-3H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]azanediyl]di(propane-3,1-diyl)]bis(phosphonic acid)
-
 Escherichia coli

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
2.4.2.8 0.0125
-
 hypoxanthine pH 7.4, 25°C Escherichia coli
2.4.2.8 0.294
-
 guanine pH 7.4, 25°C Escherichia coli
2.4.2.22 0.0043
-
 xanthine pH and temperature not specified in the publication Escherichia coli
2.4.2.22 0.091
-
 hypoxanthine pH and temperature not specified in the publication Escherichia coli

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
2.4.2.8 Mg2+ dependent on, binding structures in presence of different inhibitors, overview Escherichia coli
2.4.2.22 Mg2+ dependent on Escherichia coli

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.4.2.8 hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate Escherichia coli
-
 IMP + diphosphate
-
 ?
2.4.2.22 guanine + 5-phospho-alpha-D-ribose 1-diphosphate Escherichia coli
-
 GMP + diphosphate
-
 r
2.4.2.22 xanthine + 5-phospho-alpha-D-ribose 1-diphosphate Escherichia coli
-
 XMP + diphosphate
-
 r

Organism

EC Number Organism UniProt Comment Textmining
2.4.2.8 Escherichia coli P0A9M2
-
-
2.4.2.22 Escherichia coli P0A9M5
-
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.4.2.8 guanine + 5-phospho-alpha-D-ribose 1-diphosphate low activity Escherichia coli GMP + diphosphate
-
 r
2.4.2.8 hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
-
 Escherichia coli IMP + diphosphate
-
 ?
2.4.2.8 additional information hypoxanthine phosphoribosyltransferase (EcHPRT) has a strong preference for hypoxanthine as the base substrate Escherichia coli ?
-
-
2.4.2.22 guanine + 5-phospho-alpha-D-ribose 1-diphosphate
-
 Escherichia coli GMP + diphosphate
-
 r
2.4.2.22 hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate low activity, reaction of EC 2.4.2.8 Escherichia coli IMP + diphosphate
-
 r
2.4.2.22 additional information Escherichia coli xanthine-guanine phosphoribosyltransferase (EcXGPRT) prefers guanine and xanthine Escherichia coli ?
-
-
2.4.2.22 xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
-
 Escherichia coli XMP + diphosphate
-
 r

Synonyms

EC Number Synonyms Comment Organism
2.4.2.8 EcHPRT
-
 Escherichia coli
2.4.2.22 EcXGPRT
-
 Escherichia coli
2.4.2.22 More see also EC 2.4.2.8 Escherichia coli
2.4.2.22 xanthine-guanine PRT
-
 Escherichia coli

Ki Value [mM]

EC Number Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
2.4.2.8 0.00075
-
 9-[(N-phosphonoethyl-N-phosphonoethoxyethyl)-2-aminoethyl]-hypoxanthine 0.1 M Tris-HCl, 12 mM MgCl2, pH 7.4, 25°C Escherichia coli
2.4.2.8 0.0008
-
 [[2-[(6-oxo-1,6-dihydro-9H-purin-9-yl)methyl]propane-1,3-diyl]bis(oxymethylene)]bis(phosphonic acid) 0.1 M Tris-HCl, 12 mM MgCl2, pH 7.4, 25°C Escherichia coli
2.4.2.8 0.0014
-
 (2-[[2-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)ethyl][2-(2-phosphonoethoxy)ethyl]amino]ethyl)phosphonic acid 0.1 M Tris-HCl, 12 mM MgCl2, pH 7.4, 25°C Escherichia coli
2.4.2.8 0.00167
-
 9-[(N-phosphonoethyl-N-phosphonomethoxyethyl)-2-aminoethyl]hypoxanthine 0.1 M Tris-HCl, 12 mM MgCl2, pH 7.4, 25°C Escherichia coli
2.4.2.8 0.0028
-
 [[[(4-oxo-4,5-dihydro-3H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]azanediyl]di(propane-3,1-diyl)]bis(phosphonic acid) 0.1 M Tris-HCl, 12 mM MgCl2, pH 7.4, 25°C Escherichia coli
2.4.2.8 0.0134
-
 9-[(N-phosphonoethyl-N-phosphonobutyl)-2-aminoethyl]hypoxanthine 0.1 M Tris-HCl, 12 mM MgCl2, pH 7.4, 25°C Escherichia coli
2.4.2.8 0.017
-
 monophosphonate-2-(phosphonoethoxy)ethyl hypoxanthine pH and temperature not specified in the publication Escherichia coli
2.4.2.8 0.0218
-
 9-[(N-phosphonoethyl-N-phosphonomethyl)-2-aminoethyl]-hypoxanthine 0.1 M Tris-HCl, 12 mM MgCl2, pH 7.4, 25°C Escherichia coli
2.4.2.8 0.037
-
 (2-[(2,3-dihydroxypropyl)[2-(6-oxo-1,6-dihydro-9H-purin-9-yl)ethyl]amino]ethyl)phosphonic acid 0.1 M Tris-HCl, 12 mM MgCl2, pH 7.4, 25°C Escherichia coli
2.4.2.8 0.247
-
 IMP pH 7.4, 25°C Escherichia coli
2.4.2.8 0.526
-
 GMP pH 7.4, 25°C Escherichia coli

General Information

EC Number General Information Comment Organism
2.4.2.8 metabolism in Escherichia coli, the purine salvage pathway has two 6-oxopurine phosphoribosyltransferases (PRTs), xanthine-guanine PRT (EcXGPRT, EC 2.4.2.22) and hypoxanthine PRT (EcHPRT, EC 2.4.2.8). Escherichia coli can utilize both purine salvage and de novo pathways for the production of the nucleoside monophosphates required for incorporation into DNA and RNA. Escherichia coli is highly unusual in that it is one of only a few organisms that possess two distinct salvage enzymes for 6-oxopurine nucleoside monophosphate production Escherichia coli
2.4.2.22 metabolism in Escherichia coli, the purine salvage pathway has two 6-oxopurine phosphoribosyltransferases (PRTs), xanthine-guanine PRT (EcXGPRT, EC 2.4.2.22) and hypoxanthine PRT (EcHPRT, EC 2.4.2.8). Escherichia coli can utilize both purine salvage and de novo pathways for the production of the nucleoside monophosphates required for incorporation into DNA and RNA. Escherichia coli is highly unusual in that it is one of only a few organisms that possess two distinct salvage enzymes for 6-oxopurine nucleoside monophosphate production Escherichia coli

kcat/KM [mM/s]

EC Number kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
2.4.2.8 0.0049
-
 hypoxanthine pH 7.4, 25°C Escherichia coli
2.4.2.22 0.0012
-
 xanthine pH and temperature not specified in the publication Escherichia coli
2.4.2.22 0.0065
-
 guanine pH and temperature not specified in the publication Escherichia coli