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Literature summary for 2.4.2.8 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
Search for more literature for 2.4.2.8

Application

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

Crystallization (Commentary)

Crystallization (Comment) Organism
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

Inhibitors Comment Organism Structure
(2-[(2,3-dihydroxypropyl)[2-(6-oxo-1,6-dihydro-9H-purin-9-yl)ethyl]amino]ethyl)phosphonic acid
-
 Escherichia coli
(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-((2,3-dihydroxypropyl)(2-(hypoxanthin-9-yl)ethyl)-amino)ethyl phosphonate weak inhibition Escherichia coli
9-[(N-phosphonoethyl-N-phosphonobutyl)-2-aminoethyl]hypoxanthine
-
 Escherichia coli
9-[(N-phosphonoethyl-N-phosphonoethoxyethyl)-2-aminoethyl]-hypoxanthine
-
 Escherichia coli
9-[(N-phosphonoethyl-N-phosphonomethoxyethyl)-2-aminoethyl]hypoxanthine
-
 Escherichia coli
9-[(N-phosphonoethyl-N-phosphonomethyl)-2-aminoethyl]-hypoxanthine
-
 Escherichia coli
GMP competitive inhibitor Escherichia coli
IMP competitive inhibitor Escherichia coli
monophosphonate-2-(phosphonoethoxy)ethyl hypoxanthine PEEHx Escherichia coli
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-[(6-oxo-1,6-dihydro-9H-purin-9-yl)methyl]propane-1,3-diyl]bis(oxymethylene)]bis(phosphonic acid)
-
 Escherichia coli
[[[(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]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.0125
-
 hypoxanthine pH 7.4, 25°C Escherichia coli
0.294
-
 guanine pH 7.4, 25°C Escherichia coli

Metals/Ions

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

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate Escherichia coli
-
 IMP + diphosphate
-
 ?

Organism

Organism UniProt Comment Textmining
Escherichia coli P0A9M2
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
guanine + 5-phospho-alpha-D-ribose 1-diphosphate low activity Escherichia coli GMP + diphosphate
-
 r
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
-
 Escherichia coli IMP + diphosphate
-
 ?
additional information hypoxanthine phosphoribosyltransferase (EcHPRT) has a strong preference for hypoxanthine as the base substrate Escherichia coli ?
-
-

Synonyms

Synonyms Comment Organism
EcHPRT
-
 Escherichia coli

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
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
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
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
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
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
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
0.017
-
 monophosphonate-2-(phosphonoethoxy)ethyl hypoxanthine pH and temperature not specified in the publication Escherichia coli
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
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
0.247
-
 IMP pH 7.4, 25°C Escherichia coli
0.526
-
 GMP pH 7.4, 25°C Escherichia coli

General Information

General Information Comment Organism
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]

kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
0.0049
-
 hypoxanthine pH 7.4, 25°C Escherichia coli