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Literature summary for 2.4.2.7 extracted from

  • Ozeir, M.; Huyet, J.; Burgevin, M.C.; Pinson, B.; Chesney, F.; Remy, J.M.; Siddiqi, A.R.; Lupoli, R.; Pinon, G.; Saint-Marc, C.; Gibert, J.F.; Morales, R.; Ceballos-Picot, I.; Barouki, R.; Daignan-Fornier, B.; Olivier-Bandini, A.; Auge, F.; Nioche, P.
    Structural basis for substrate selectivity and nucleophilic substitution mechanisms in human adenine phosphoribosyltransferase catalyzed reaction (2019), J. Biol. Chem., 294, 11980-11991 .
    View publication on PubMedView publication on EuropePMC

Crystallization (Commentary)

Crystallization (Comment) Organism
enzyme complexes phosphate-hAPRT, hypoxanthine-PRPP-Mg2+-hAPRT, IMP-hAPRT, and GMP-hAPRT, mixing of 400 nl of 5 mg/ml protein complexes in 20 mM Tris-HCl, pH 7.4, 5 mM MgCl2, with 200 nl of crystallization solution made of 85 mM Tris-HCl, pH 8.5, 170 mM NaOAc, 19-21% PEG 4000, and 0-30% glycerol, overnight at 20°C, X-ray diffraction structrue determination and analysis at resolution 1.55-1.90 A, molecular replacement using the structure with PDB ID 6FCH as template, and modeling Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
additional information
-
additional information Michaelis-Menten kinetics Homo sapiens

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required, enzyme binding structure, overview Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
adenine + 5-phospho-alpha-D-ribose 1-diphosphate Homo sapiens
-
AMP + diphosphate
-
r

Organism

Organism UniProt Comment Textmining
Homo sapiens P07741
-
-

Reaction

Reaction Comment Organism Reaction ID
AMP + diphosphate = adenine + 5-phospho-alpha-D-ribose 1-diphosphate molecular reaction mechanism in both directions of the reaction for hAPRT: in the forward reaction, SN2-type molecular mechanism including some SN1 characteristics, and in the reverse reaction, a proposed magnesium-assisted SN2-type mechanism, detailed overview Homo sapiens

Source Tissue

Source Tissue Comment Organism Textmining
commercial preparation
-
Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
adenine + 5-phospho-alpha-D-ribose 1-diphosphate
-
Homo sapiens AMP + diphosphate
-
r
adenine + 5-phospho-alpha-D-ribose 1-diphosphate binding to hAPRT is substrate shape-specific in the forward reaction, whereas it is base-specific in the reverse reaction Homo sapiens AMP + diphosphate
-
r
additional information although hypoxanthine and adenine have the same chemical skeleton, which differs only by a hydroxyl instead of an amine at the C6 position away from the reactive N9 nitrogen, adenine seems to be the only purine metabolized by hAPRT Homo sapiens ?
-
-

Synonyms

Synonyms Comment Organism
APRT
-
Homo sapiens
hAPRT
-
Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
23
-
assay at Homo sapiens

Temperature Stability [°C]

Temperature Stability Minimum [°C] Temperature Stability Maximum [°C] Comment Organism
47.6
-
unfolding temperature of enzyme hAPRT with hypoxanthine Homo sapiens
49.6
-
unfolding temperature of enzyme hAPRT Homo sapiens
50.3
-
unfolding temperature of enzyme hAPRT with adenine Homo sapiens
51.2
-
unfolding temperature of enzyme hAPRT with IMP Homo sapiens
52.1
-
unfolding temperature of enzyme hAPRT with diphosphate Homo sapiens
53
-
unfolding temperature of enzyme hAPRT with GMP Homo sapiens
53.5
-
unfolding temperature of enzyme hAPRT with diphosphate and IMP Homo sapiens
53.6
-
unfolding temperature of enzyme hAPRT with diphosphate and GMP Homo sapiens
59
-
unfolding temperature of enzyme hAPRT with AMP Homo sapiens
64.3
-
unfolding temperature of enzyme hAPRT with diphosphate and AMP Homo sapiens
79.6
-
unfolding temperature of enzyme hAPRT with PRPP Homo sapiens
79.7
-
unfolding temperature of enzyme hAPRT with PRPP and hypoxanthine Homo sapiens
79.9
-
unfolding temperature of enzyme hAPRT with PRPP and adenine Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.5
-
assay at Homo sapiens

General Information

General Information Comment Organism
metabolism the reversible adenine phosphoribosyltransferase enzyme (APRT) is essential for purine homeostasis in prokaryotes and eukaryotes. In humans, APRT (hAPRT) is the only enzyme known to produce AMP in cells from dietary adenine. APRT can also process adenine analogues, which are involved in plant development or neuronal homeostasis Homo sapiens
additional information analysis of the molecular mechanism underlying substrate specificity of APRT and catalysis in both directions of the reaction. Comparison of the crystal structures of hAPRT complexed to three cellular nucleotide analogues (hypoxanthine, IMP, and GMP) with the phosphate-bound enzyme. Substrate shape recognition in the forward reaction, purine base recognition in the reverse reaction. Binding to hAPRT is substrate shape-specific in the forward reaction, whereas it is base-specific in the reverse reaction. Quantum mechanics/molecular mechanics (QM/MM) analysis suggests that the forward reaction is mainly a nucleophilic substitution of type 2 (SN2) with a mix of SN1-type molecular mechanism. Based on our structural analysis, a magnesium-assisted SN2-type mechanism is involved in the reverse reaction. Structure-function analysis, overview Homo sapiens