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Literature summary extracted from

  • Harijan, R.K.; Zoi, I.; Antoniou, D.; Schwartz, S.D.; Schramm, V.L.
    Catalytic-site design for inverse heavy-enzyme isotope effects in human purine nucleoside phosphorylase (2017), Proc. Natl. Acad. Sci. USA, 114, 6456-6461 .
    View publication on PubMedView publication on EuropePMC

Protein Variants

EC Number Protein Variants Comment Organism
2.4.2.1 F159Y site-directed mutagenesis, pre-steadystate chemistry is reduced 32fold in mutant F159Y PNP. Pre-steady-state chemistry compares heavy and light molecular weight wild-type and mutant F159Y PNPs and finds a normal heavy-enzyme isotope effect of 1.31 for wild-type PNP and an inverse effect of 0.75 for F159Y mutant PNP. Increased isotopic mass in F159Y PNP causes more efficient transition state formation. Most heavy enzymes demonstrate normal heavy-enzyme isotope effects, and F159Y PNP is a rare example of an inverse effect Homo sapiens

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
2.4.2.1 additional information
-
additional information steady-state Michaelis-Menten kinetics for the light- and heavy-isotope-labeled PNPs are measured for guanosine phosphorolysis, single-turnover pre-steady-state constants. Detailed isotope and kinetic analysis of wild-type an dmutant F159Y mutant enzymes, overview Homo sapiens
2.4.2.1 0.0341
-
guanosine pH 7.4, 25°C, wild-type light PNP Homo sapiens
2.4.2.1 0.0399
-
guanosine pH 7.4, 25°C, wild-type heavy PNP Homo sapiens
2.4.2.1 0.0542
-
guanosine pH 7.4, 25°C, mutant F159Y heavy PNP Homo sapiens
2.4.2.1 0.0564
-
guanosine pH 7.4, 25°C, mutant F159Y light PNP Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.4.2.1 guanosine + phosphate Homo sapiens
-
guanine + alpha-D-ribose 1-phosphate
-
r

Organism

EC Number Organism UniProt Comment Textmining
2.4.2.1 Homo sapiens P00491
-
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.4.2.1 guanosine + phosphate
-
Homo sapiens guanine + alpha-D-ribose 1-phosphate
-
r

Synonyms

EC Number Synonyms Comment Organism
2.4.2.1 PNP
-
Homo sapiens
2.4.2.1 purine nucleoside phosphorylase
-
Homo sapiens

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
2.4.2.1 25
-
assay at Homo sapiens

Turnover Number [1/s]

EC Number Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
2.4.2.1 7.8
-
guanosine pH 7.4, 25°C, wild-type heavy PNP Homo sapiens
2.4.2.1 8.3
-
guanosine pH 7.4, 25°C, mutant F159Y heavy PNP Homo sapiens
2.4.2.1 8.5
-
guanosine pH 7.4, 25°C, mutant F159Y light PNP Homo sapiens
2.4.2.1 8.7
-
guanosine pH 7.4, 25°C, wild-type light PNP Homo sapiens

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
2.4.2.1 7.4
-
assay at Homo sapiens

General Information

EC Number General Information Comment Organism
2.4.2.1 malfunction human genetic deficiency of PNP impairs expansion of activated T-cells as a consequence of the accumulation of dGTP specifically in activated T-cells. An unbalanced deoxynucleotide triphosphate pool leads to apoptotic cell death in the activated T-cell population, with no effect on quiescent T-cells. The inhibition of PNP is reported to be therapeutic in T-cell lymphoma and gout disease in clinical trials Homo sapiens
2.4.2.1 additional information crystal structures and TPS dynamics of native and F159Y PNPs explore the catalytic-site geometry associated with these catalytic changes. Experimental validation of transition path-sampling (TPS) predictions for barrier crossing establishes the connection of rapid protein dynamics and vibrational coupling to enzymatic transition state passage Homo sapiens
2.4.2.1 physiological function enzyme PNP provides the only metabolic pathway for the degradation of 2'-deoxyguanosine in human cells Homo sapiens

kcat/KM [mM/s]

EC Number kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
2.4.2.1 150.7
-
guanosine pH 7.4, 25°C, mutant F159Y light PNP Homo sapiens
2.4.2.1 153.1
-
guanosine pH 7.4, 25°C, mutant F159Y heavy PNP Homo sapiens
2.4.2.1 195.5
-
guanosine pH 7.4, 25°C, wild-type heavy PNP Homo sapiens
2.4.2.1 255.1
-
guanosine pH 7.4, 25°C, wild-type light PNP Homo sapiens