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evolution
in some organisms, like Escherichia coli, two distinct forms of PNP exist, with markedly different structure and substrate specificity. The second form, the so-called E. coli PNP-II, is sometimes referred to as xanthosine phosphorylase, since it is inducible by this nucleoside, but its specificity is not limited to this compound, and includes guanosine, inosine and nicotinamide riboside
evolution
in some organisms, like Escherichia coli, two distinct forms of PNP exist, with markedly different structure and substrate specificity. The second form, the so-called Escherichia coli PNP-II, is sometimes referred to as xanthosine phosphorylase, since it is inducible by this nucleoside, but its specificity is not limited to this compound, and includes guanosine, inosine and nicotinamide riboside
evolution
most PNPs are divided into trimeric PNPs and hexametric PNPs based on molecular mass, protein structure, or substrate specificity
evolution
the enzyme belongs to the type I PNP family of hexameric enzymes
evolution
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the homodimeric PNP from Ervinia carotovora cannot be assigned to the two described PNP classes, trimeric and hexameric PNPs
evolution
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the homotetrameric PNP from Baccilus cereus cannot be assigned to the two described PNP classes, trimeric and hexameric PNPs
evolution
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the pentameric PNP from Plasmodium lophurae cannot be assigned to the two described PNP classes, trimeric and hexameric PNPs
evolution
the PNP from Cellulomonas sp. cannot be assigned to the any of two described PNP classes, trimeric and hexameric PNPs
evolution
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the PNP from Thermus thermophilus cannot be assigned to the any of two described PNP classes, trimeric and hexameric PNPs
evolution
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most PNPs are divided into trimeric PNPs and hexametric PNPs based on molecular mass, protein structure, or substrate specificity
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malfunction
the salT-deficient mutant strain shows reduced salinosporamide A and salinosporamide B synthesis
malfunction
effect of remote mutations on the thermodynamic activation parameters of human purine nucleoside phosphorylase, overview. More than 2700 independent reaction free energy profiles for six different temperatures are calculated to obtain high-precision computational Arrhenius plots. On the basis of these, the activation enthalpies and entropies are computed from linear regression of the plots with DELTAG++ as a function of 1/T to obtain thermodynamic activation parameters. The substrate specificity is related to the difference in thermodynamic activation parameters. Remote mutations affect the activation enthalpy-entropy balance
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
malfunction
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substrate specificity of trimeric and hexameric PNPs may be changed by mutations of the crucial active site amino acids, namely Asp in hexameric PNPs and Asn in trimeric PNPs
malfunction
substrate specificity of trimeric and hexameric PNPs may be changed by mutations of the crucial active site amino acids, namely Asp in hexameric PNPs and Asn in trimeric PNPs
malfunction
substrate specificity of trimeric and hexameric PNPs may be changed by mutations of the crucial active site amino acids, namely Asp in hexameric PNPs and Asn in trimeric PNPs
malfunction
substrate specificity of trimeric and hexameric PNPs may be changed by mutations of the crucial active site amino acids, namely Asp in hexameric PNPs and Asn in trimeric PNPs
malfunction
substrate specificity of trimeric and hexameric PNPs may be changed by mutations of the crucial active site amino acids, namely Asp in hexameric PNPs and Asn in trimeric PNPs
metabolism
the enzyme is involved in the chloroethylmalonyl-CoA biosynthetic pathway, overview
metabolism
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comparison of growth characteristics including intracellular protein levels, RNA content, and nucleotide pool sizes between the extreme halophile Halobacterium halobium and the moderate halophile Haloferax volcanii. The differences in the metabolism of purine bases and nucleosides and the sensitivity to purine analogs between the two halobacteria are reflected in differences in purine enzyme levels
metabolism
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comparison of growth characteristics including intracellular protein levels, RNA content, and nucleotide pool sizes between the extreme halophile Halobacterium halobium and the moderate halophile Haloferax volcanii. The differences in the metabolism of purine bases and nucleosides and the sensitivity to purine analogs between the two halobacteria are reflected in differences in purine enzyme levels
metabolism
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key enzyme in ribavirin metabolism of the human small intestine
metabolism
nucleoside phosphorylases (NPs) catalyze the reversible cleavage of the glycosidic bond of (deoxy)ribonucleosides in the presence of phosphate to generate a nucleobase and alpha-D-(deoxy)ribose-1-phosphate. NPs include pyrimidine NPs (PyNPs, EC 2.4.2.2) and purine NPs (PNPs, EC 2.4.2.1). PyNPs show substrate specificity for the phosphorolysis of pyrimidine nucleosides, while PNPs are specific for purine nucleoside substrates
metabolism
PNPs play a key role in the purine salvage pathway
metabolism
purine nucleoside phosphorylase (PNP) from Kluyveromyces lactis (KlacPNP) is a key enzyme involved in the purine degradation pathway, overview
metabolism
purine nucleoside phosphorylase (PNP) is a crucial enzyme that participates in the metabolism of purines in nucleoside salvage pathway
metabolism
the enzyme is involved in the purine metabolism in Plasmodium falciparum
metabolism
the purine metabolism in Helicobacter pylori is solely dependant on the salvage pathway and one of the key enzymes in this pathway is purine nucleoside phosphorylase (PNP)
metabolism
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purine nucleoside phosphorylase (PNP) from Kluyveromyces lactis (KlacPNP) is a key enzyme involved in the purine degradation pathway, overview
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metabolism
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purine nucleoside phosphorylase (PNP) from Kluyveromyces lactis (KlacPNP) is a key enzyme involved in the purine degradation pathway, overview
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metabolism
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purine nucleoside phosphorylase (PNP) from Kluyveromyces lactis (KlacPNP) is a key enzyme involved in the purine degradation pathway, overview
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metabolism
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purine nucleoside phosphorylase (PNP) from Kluyveromyces lactis (KlacPNP) is a key enzyme involved in the purine degradation pathway, overview
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metabolism
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purine nucleoside phosphorylase (PNP) from Kluyveromyces lactis (KlacPNP) is a key enzyme involved in the purine degradation pathway, overview
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metabolism
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nucleoside phosphorylases (NPs) catalyze the reversible cleavage of the glycosidic bond of (deoxy)ribonucleosides in the presence of phosphate to generate a nucleobase and alpha-D-(deoxy)ribose-1-phosphate. NPs include pyrimidine NPs (PyNPs, EC 2.4.2.2) and purine NPs (PNPs, EC 2.4.2.1). PyNPs show substrate specificity for the phosphorolysis of pyrimidine nucleosides, while PNPs are specific for purine nucleoside substrates
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metabolism
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purine nucleoside phosphorylase (PNP) from Kluyveromyces lactis (KlacPNP) is a key enzyme involved in the purine degradation pathway, overview
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physiological function
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parasites lacking purine nucelotide phosphorylase due to gene disruption are attenuated and clear in mice. Although able to form gametocytes, purine nucelotide phosphorylase-deficient parasites do not form oocysts in mosquito midguts and are not transmitted from mosquitoes to mice. Mice given purine nucelotide phosphorylase-deficient parasites are immune to subsequent challenge to a lethal inoculum of Plasmodium yoelii YM and to challenge from strain Plasmodium yoelii 17XNL
physiological function
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part of 4-fluorothreonine biosynthesis
physiological function
targeted gene disruption results in loss of enzyme activity in lysate, with normal activity of adenosine deaminase. Mutant parasites show a greater requirement for exogenous purines and a severe growth defect at physiological concentrations of hypoxanthine. The mutant parasites are more sensitive to purine nucleoside phosphorylase inhibitors that bind human purine nucelotide phosphorylase tighter and less sensitive to inhibitor 5'-methylthio-immucillin-H
physiological function
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the enzyme is active in tubers as a negative regulator of cytokinins, prolonging endodormancy by a chill-reversible mechanism
physiological function
enzyme PNP provides the only metabolic pathway for the degradation of 2'-deoxyguanosine in human cells
physiological function
Escherichia coli PNP converts pro-drugs, which are relative nontoxic purine nucleosides (for example 6-methyl purine 2'-deoxynucleoside or fludarabine), to their respective purine analogues (here, to 6-methylpurine and 2-fluoroadenine, respectively), which are very potent, toxic drugs
physiological function
PNP catalyzes a reversible phosphorolysis of the N-glycosidic bond in natural purine nucleosides, as well as inmany purine analogs, some of them displaying marked biological and pharmacological activity
physiological function
PNP catalyzes a reversible phosphorolysis of the N-glycosidic bond in natural purine nucleosides, as well as inmany purine analogues, some of them displaying marked biological and pharmacological activity
physiological function
PNP catalyzes a reversible phosphorolysis of the N-glycosidic bond in natural purine nucleosides, as well as inmany purine analogues, some of them displaying marked biological and pharmacological activity
physiological function
PNP is the key enzyme in the purine salvage pathway. It catalyses the reversible phosphorolytic cleavage of the glycosidic bond of purine nucleosides (and some analogues) in the presence of phosphate as a second substrate
physiological function
purine nucleoside phosphorylase (PNP) catalyzes the reversible cleavage of the glycosidic bond of ribo- and 2'-deoxyribonucleosides, yielding the corresponding purine base and (2'-deoxy)ribose 1-phosphate as products. Enzyme HsPNP belongs to the low-molecular mass (low-mm) family of PNPs that generally are specific toward 6-oxopurines, e.g. inosine (INO) and guanosine (GUO), and thus are frequently termed Ino-Guo phosphorylases
physiological function
purine nucleoside phosphorylases (PNPs) catalyze the reversible phosphorolysis of nucleosides and are key enzymes involved in nucleotide metabolism. They are essential for normal cell function and can catalyze the transglycosylation
physiological function
the enzyme catalyzes the reversible phosphorolysis of purine ribonucleosides
physiological function
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PNP catalyzes a reversible phosphorolysis of the N-glycosidic bond in natural purine nucleosides, as well as inmany purine analogues, some of them displaying marked biological and pharmacological activity
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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
additional information
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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
additional information
effect of heavy isotope labeling on the reaction catalyzed by human purine nucleoside phosphorylase (hPNP) to elucidate the origin of its catalytic effect and of the enzymatic kinetic isotope effect (EKIE). Using quantum mechanical and molecular mechanical (QM/MM) molecular dynamics (MD) simulations, the mechanism of the hPNP enzymeis investigated and the dynamic effects by means of the calculation of the recrossing transmission coefficient. The simulations reveal that the chemical reaction is slightly slower in the heavy enzyme than in its light counterpart enzyme because protein motions coupled to the reaction coordinate are slower. Thus, protein dynamics have a small but measurable effect on the chemical reaction rate
additional information
enzyme kinetics, ligand binding, docking, and molecular dynamics simulation studies, overview. Active site structure and ligand binding structure analysis. HpPNP has low affinity towards the natural substrate adenosine. Molecular dynamics simulations show that Pi moves out of most active sites, in accordance with its weak binding. Conformational changes between nonstandard and standard binding modes of nucleoside are observed during the simulations. The protonation of the purine base at position N(7) by the side chain of Asp204 is the first step in the catalytic cleavage of the glycosidic bond. Hence, 7-methylguanosine bears one feature of the transition state and does not need to be protonated
additional information
KlacPNP and KlacPNPN256D reduce purine content in a beer sample
additional information
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KlacPNP and KlacPNPN256D reduce purine content in a beer sample
additional information
N6-etheno-ATP and its downstream metabolites are devoid of pharmacological activity
additional information
possible tautomeric forms of 1,N6-etheno-isoguanine. The main reason for slow ribosylation and the resistance of the parent N2,3-ethenoguanine to the enzymatic ribosylation is probably unfavorable energetics
additional information
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possible tautomeric forms of 1,N6-etheno-isoguanine. The main reason for slow ribosylation and the resistance of the parent N2,3-ethenoguanine to the enzymatic ribosylation is probably unfavorable energetics
additional information
results from molecular modeling reveal that there are two binding sites, i.e. active site (major) and tryptophan site (minor) on PNP. Analysis of structure-activity relationship, computational modeling, binding structure in the active site, overview
additional information
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results from molecular modeling reveal that there are two binding sites, i.e. active site (major) and tryptophan site (minor) on PNP. Analysis of structure-activity relationship, computational modeling, binding structure in the active site, overview
additional information
superposition of the bioactive conformations of 5'-methylthioimmucillin-H (PDB ID 1Q1G) and DADMe-immucillin-G (PDB ID 3PHC)
additional information
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superposition of the bioactive conformations of 5'-methylthioimmucillin-H (PDB ID 1Q1G) and DADMe-immucillin-G (PDB ID 3PHC)
additional information
the enzyme-catalyzed reaction involves the proton transfer from the carboxyl group of Asp204 to the nitrogen atom N7 of the purine base. This process is accompanied by conformational changes. The C-terminal alpha-helix (214-236) is divided by a gamma-turn into two helices (214-219 and 223-236), resulting in the residue Arg217 coming closer to Asp204, and the active site adopts a closed conformation. Upon phosphate binding, the position of the residue Arg24 is fixed via a hydrogen bond with Arg217 (NE_Arg2-O_Arg217). The key role of the residues Asp204, Arg217, and Arg24 in the catalytic activity is confirmed by the replacement of these residues with alanine. These replacements lead to a substantial decrease in the activity toward natural substrates
additional information
the structure of Helicobacter pylori PNP is typical for high molecular mass PNPs. Active site structure and ligand binding structure analysis, overview. The structure of Helicobacter pylori PNP-Zg represents the first reported case of a true dead-end complex of bacterial hexameric PNP bound with one of the reaction substrates, phosphate, and one of the reaction products, hypoxanthine, which is produced by the enzyme turnover during the purification procedure
additional information
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the structure of Helicobacter pylori PNP is typical for high molecular mass PNPs. Active site structure and ligand binding structure analysis, overview. The structure of Helicobacter pylori PNP-Zg represents the first reported case of a true dead-end complex of bacterial hexameric PNP bound with one of the reaction substrates, phosphate, and one of the reaction products, hypoxanthine, which is produced by the enzyme turnover during the purification procedure
additional information
the substrate specificity is related to the difference in thermodynamic activation parameters. Furthermore, the calculations show that the human PNP specificity for 6-oxopurines over 6-aminopurines originates from significant differences in electrostatic preorganization. Residues Y88, F200, E201, N243, and H257 interact with the nucleoside while S33, H64, R84, A116, S220, and two conserved waters interacting with the phosphate group are identified as key catalytic site residues. In addition, F159* from one adjacent subunit is oriented in the active site so that it makes contact with the nucleoside and shields it from the solvent
additional information
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the substrate specificity is related to the difference in thermodynamic activation parameters. Furthermore, the calculations show that the human PNP specificity for 6-oxopurines over 6-aminopurines originates from significant differences in electrostatic preorganization. Residues Y88, F200, E201, N243, and H257 interact with the nucleoside while S33, H64, R84, A116, S220, and two conserved waters interacting with the phosphate group are identified as key catalytic site residues. In addition, F159* from one adjacent subunit is oriented in the active site so that it makes contact with the nucleoside and shields it from the solvent
additional information
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KlacPNP and KlacPNPN256D reduce purine content in a beer sample
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additional information
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KlacPNP and KlacPNPN256D reduce purine content in a beer sample
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additional information
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KlacPNP and KlacPNPN256D reduce purine content in a beer sample
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additional information
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KlacPNP and KlacPNPN256D reduce purine content in a beer sample
-
additional information
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enzyme kinetics, ligand binding, docking, and molecular dynamics simulation studies, overview. Active site structure and ligand binding structure analysis. HpPNP has low affinity towards the natural substrate adenosine. Molecular dynamics simulations show that Pi moves out of most active sites, in accordance with its weak binding. Conformational changes between nonstandard and standard binding modes of nucleoside are observed during the simulations. The protonation of the purine base at position N(7) by the side chain of Asp204 is the first step in the catalytic cleavage of the glycosidic bond. Hence, 7-methylguanosine bears one feature of the transition state and does not need to be protonated
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additional information
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KlacPNP and KlacPNPN256D reduce purine content in a beer sample
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additional information
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enzyme kinetics, ligand binding, docking, and molecular dynamics simulation studies, overview. Active site structure and ligand binding structure analysis. HpPNP has low affinity towards the natural substrate adenosine. Molecular dynamics simulations show that Pi moves out of most active sites, in accordance with its weak binding. Conformational changes between nonstandard and standard binding modes of nucleoside are observed during the simulations. The protonation of the purine base at position N(7) by the side chain of Asp204 is the first step in the catalytic cleavage of the glycosidic bond. Hence, 7-methylguanosine bears one feature of the transition state and does not need to be protonated
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additional information
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KlacPNP and KlacPNPN256D reduce purine content in a beer sample
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additional information
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N6-etheno-ATP and its downstream metabolites are devoid of pharmacological activity
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