Affinage

Showing PNP — NP is a alias.

PNP

Pancreatic polypeptide prohormone · UniProt P01298

Length
95 aa
Mass
10.4 kDa
Annotated
2026-06-10
100 papers in source corpus 19 papers cited in narrative 19 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PNP is a cytoplasmic homotrimeric enzyme that catalyzes the phosphorolysis of 6-oxopurine nucleosides in the beta-configuration, recognizing the N1 and O6 positions of the purine ring as essential determinants of substrate activity, with a conserved active-site glutamate (Glu201, equivalent to Glu204 in the bacterial enzyme) serving the key catalytic role and a neighboring asparagine supporting binding of 6-oxopurines rather than catalysis (PMID:2109978, PMID:10600382, PMID:15983407). The dianionic form of inorganic phosphate is the preferred cosubstrate, and the enzyme exhibits negative cooperativity in phosphate binding, indicating allosteric communication between active sites (PMID:17639373). Catalysis is accompanied by ordering of a dynamic loop (residues 243–266) near the purine base upon substrate or inhibitor binding, with active-site loops coexisting in multiple conformational states in the phosphate-bound enzyme that collapse to single conformations upon transition-state-analog binding (PMID:18269249, PMID:23438750). In T cells, PNP activity is essential for purine metabolism and dGTP homeostasis: enzymatic inhibition combined with deoxyguanosine drives massive dGTP accumulation that inhibits ribonucleotide reductase and triggers caspase-3-mediated apoptosis, selectively killing T-lineage leukemic cells—a vulnerability exploited by transition-state-analog inhibitors such as immucillin-H/forodesine whose binding is defined by human PNP crystal structures (PMID:13679061, PMID:12781704, PMID:9403342). A loss-of-function PNP variant (rs1049564) produces relative PNP deficiency, an S-phase cell cycle block reversible by hypoxanthine and adenosine, and increased type I interferon pathway activation (PMID:28859258). Beyond its canonical cytoplasmic role, PNP is constitutively released into the extracellular medium where it contributes to purinergic homeostasis, and the C. elegans ortholog pnp-1 acts in intestinal epithelium as a negative regulator of the intracellular pathogen response (PMID:33878133, PMID:28251649).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1990 Medium

    Established what defines a PNP substrate at the chemical level, explaining the enzyme's strict requirement for 6-oxopurine nucleosides and the basis of substrate discrimination versus the promiscuous bacterial enzyme.

    Evidence Kinetic analysis of modified nucleoside analogues with mammalian and bacterial PNP

    PMID:2109978

    Open questions at the time
    • Catalytic residue identities proposed but not confirmed by mutagenesis
    • No structural model at this stage
  2. 1997 High

    Defined the terminal effector pathway of PNP inhibition in T cells, showing that cell death proceeds through caspase-3-mediated apoptosis dependent on dGTP accumulation.

    Evidence Western blots for PARP and alpha-spectrin cleavage, caspase-3 activity assays, and deoxycytidine/pan-caspase rescue in T cells treated with CI-1000 plus deoxyguanosine

    PMID:9403342

    Open questions at the time
    • Did not quantify the dNTP pool changes upstream of apoptosis
    • Did not address selectivity for T cells over other lineages
  3. 1999 High

    Provided the first structural mechanism for purine recognition and catalysis, identifying the phosphate-binding residues and assigning the catalytic glutamate (Glu204/Glu201) and a binding-supporting asparagine.

    Evidence X-ray crystallography of binary and ternary dead-end complexes of trimeric Cellulomonas PNP at 2.2–2.4 Å

    PMID:10600382

    Open questions at the time
    • Structure from a bacterial homolog rather than human enzyme
    • Catalytic role inferred from geometry plus prior kinetics
  4. 2003 High

    Resolved the structural basis of transition-state-analog inhibition and purine binding in the human enzyme, enabling rational inhibitor design.

    Evidence X-ray crystallography of human PNP with immucillin-H and with guanine

    PMID:13679061 PMID:14680831

    Open questions at the time
    • Static snapshots did not capture loop dynamics
    • Did not quantify inhibitor potency in cells
  5. 2003 High

    Demonstrated that dGTP accumulation, not dATP, is the primary cytotoxic driver of PNP inhibition, mechanistically linking it to ribonucleotide reductase inhibition.

    Evidence dNTP pool analysis and deoxycytidine/lamivudine rescue in CEM-SS T-ALL cells treated with forodesine plus deoxyguanosine

    PMID:12781704

    Open questions at the time
    • Restricted to a single T-ALL line
    • Did not connect dGTP accumulation to the caspase cascade in the same assay
  6. 2005 High

    Refined the substrate-binding determinants of human PNP, confirming preference for beta-configuration purine nucleosides with 6-keto groups.

    Evidence X-ray crystallography of human PNP with guanosine, 3'-deoxyguanosine, 8-azaguanine and hypoxanthine complexes

    PMID:15582582 PMID:15983407

    Open questions at the time
    • Did not resolve catalytic intermediates
    • Loop dynamics not characterized
  7. 2006 Medium

    Confirmed PNP as an intracellular cytoplasmic enzyme essential for T-cell purine metabolism by restoring function in deficient cells.

    Evidence Protein transduction of PTD-PNP into PNP-deficient lymphocytes with fractionation and T-cell functional assays

    PMID:16930574

    Open questions at the time
    • Used an engineered fusion rather than endogenous protein
    • Single-lab functional correction
  8. 2008 High

    Characterized the conformational behavior of the active site, showing that the 243–266 loop becomes highly ordered upon ligand binding and that ternary complex formation does not require kinetically significant conformational changes.

    Evidence Tryptophan-free Leuko-PNP construct studied by mutagenesis, fluorescence, 13C NMR, temperature-jump, and crystallography

    PMID:18269249

    Open questions at the time
    • Conducted on an engineered Trp-to-Tyr variant
    • Did not link loop ordering to catalytic rate enhancement
  9. 2007 Medium

    Defined the phosphate cosubstrate chemistry, establishing the dianionic phosphate as preferred and revealing negative cooperativity indicative of inter-subunit allostery.

    Evidence pH-dependent enzyme kinetics and Hill coefficient analysis of human erythrocyte and E. coli PNP

    PMID:17639373

    Open questions at the time
    • Allostery inferred from kinetics without structural validation
    • Single lab
  10. 2013 High

    Showed that catalytic-site loops sample multiple conformational states in the phosphate-bound enzyme that are selected to single conformations by transition-state analogs, providing a dynamic view of inhibitor action.

    Evidence 19F-NMR with site-specific 6-fluoro-tryptophan labeling combined with X-ray crystallography of multiple ligand complexes

    PMID:23438750

    Open questions at the time
    • Required site-specific fluorine labeling
    • Functional consequence of each conformer not quantified
  11. 2017 Medium

    Linked a human loss-of-function PNP variant to cell cycle disruption and innate immune dysregulation, connecting relative PNP deficiency to S-phase block and type I IFN activation.

    Evidence Genotyped lymphoblastoid lines with enzyme assays, flow cytometry, hypoxanthine/adenosine rescue, and IFN gene expression

    PMID:28859258

    Open questions at the time
    • Single variant in a cell-line model
    • Mechanism linking purine deficiency to IFN activation not resolved
  12. 2017 Medium

    Identified an extracellular pool of enzymatically active PNP under receptor and oxygen-state control, expanding its role into purinergic system homeostasis.

    Evidence Extracellular enzyme activity detection with P2Y1/A2A agonist pharmacology and hypoxia/re-oxygenation in C6 glioma cells

    PMID:28251649

    Open questions at the time
    • Single cell model
    • Mechanism of release not defined
  13. 2011 Medium

    Implicated PNP as a downstream effector of tumor-suppressor miRNAs in prostate cancer, where its expression supports proliferation, migration, and invasion.

    Evidence miR-1/miR-133a restoration, luciferase 3'UTR reporter, and PNP siRNA knockdown with phenotypic assays in PC3/DU145 cells

    PMID:22068816

    Open questions at the time
    • Single tumor type and lab
    • Metabolic mechanism of the oncogenic phenotype not defined
  14. 2020 Low

    Positioned SAMHD1 as a resistance factor that buffers dNTP accumulation during PNP inhibition, defining a synthetic-lethal vulnerability in SAMHD1-deficient cancers.

    Evidence Cell viability assays in SAMHD1-deficient versus proficient lines treated with PNP inhibitors

    PMID:33235905

    Open questions at the time
    • Single report with limited mechanistic detail
    • Direct biochemical interaction not demonstrated
    • Not validated in vivo

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PNP's purine-base products are decoded as immune and host-defense signals—linking its catalytic output to type I IFN activation and the intracellular pathogen response—remains unresolved.
  • No defined signaling intermediate connecting purine metabolite levels to IFN induction
  • Conservation of the host-defense role to mammals untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 4 GO:0140098 catalytic activity, acting on RNA 3 GO:0016787 hydrolase activity 2
Localization
GO:0005576 extracellular region 1 GO:0005829 cytosol 1
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-168256 Immune System 2 R-HSA-5357801 Programmed Cell Death 2

Evidence

Reading pass · 19 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1990 Human and mammalian purine nucleoside phosphorylase (PNP) requires N1 and O6 of the purine ring as a binding site for phosphorolysis activity, while the bacterial (E. coli) enzyme is less specific. N7-methylation of the purine ring both labilizes the glycosidic bond and impedes protonation at N7, a postulated prerequisite for enzymatic phosphorolysis. A histidine residue is proposed to interact with N1 as a donor and O6 as an acceptor (or alternatively N1-H and C2-NH2 interact with a glutamate residue). Kinetic analysis of substrate/inhibitor properties (Km, Vmax/Km) using modified nucleoside analogues with mammalian and bacterial PNP enzymes Zeitschrift fur Naturforschung. C, Journal of biosciences Medium 2109978
1999 Crystal structure of trimeric PNP from Cellulomonas sp. revealed the phosphate binding site (Ser46, Arg103, His105, Gly135, Ser223) and that guanine is recognized via a zig-zag hydrogen-bond pattern through Glu204 (equivalent to Glu201 in human PNP). Glu204 plays the key catalytic role, while Asn246 (Asn243 in mammalian) supports binding of 6-oxopurines rather than catalysis. This mechanism explains why N7-substituted nucleosides are excellent substrates and adenosine lacks substrate activity (due to bridging of O6 via water to Asn246). X-ray crystallography of binary (enzyme + phosphate) and ternary dead-end (enzyme + phosphate + 8-iodoguanine) complexes at 2.2–2.4 Å resolution Journal of molecular biology High 10600382
2003 Crystal structure of human PNP complexed with the transition-state analog immucillin-H (ImmH) at 2.6 Å resolution established the structural basis for ImmH's high specificity and potency toward human PNP, defining the active-site interactions that differentiate it from non-T-cell targets. X-ray crystallography using synchrotron radiation Biochemical and biophysical research communications High 13679061
2003 Crystal structure of human PNP in complex with guanine at 2.7 Å resolution refined the purine-binding site residues and explained the structural differences between the apoenzyme, the guanine complex, and the immucillin-H complex, providing a more reliable model for inhibitor design. X-ray crystallography using synchrotron radiation Biochemical and biophysical research communications High 14680831
2003 PNP inhibition (BCX-1777/forodesine) combined with deoxyguanosine kills T-ALL cells by causing a 154-fold accumulation of dGTP (and 8-fold accumulation of dATP). Reversal experiments with deoxycytidine (dCyd) showed that dGTP accumulation, not dATP accumulation, is the primary cytotoxic mechanism. The mechanism involves inhibition of ribonucleotide reductase by dGTP, leading to apoptosis. Cell proliferation assays, dNTP pool analysis, rescue experiments with dCyd and lamivudine in CEM-SS T-ALL cells International immunopharmacology High 12781704
2005 Crystal structures of human PNP in complex with guanosine (2.80 Å), 3'-deoxyguanosine (2.86 Å), and 8-azaguanine (2.85 Å) further defined the substrate-binding site and the enzyme's preference for purine nucleosides in the beta-configuration with 6-keto groups. X-ray crystallography using synchrotron radiation Acta crystallographica. Section D, Biological crystallography High 15983407
2005 Crystal structure of human PNP complexed with hypoxanthine at 2.6 Å resolution characterized the intermolecular interactions between the ligand and the active site, contributing to the structural model of the purine-binding site. X-ray crystallography Biochemical and biophysical research communications Medium 15582582
2008 Tryptophan-free human PNP (Leuko-PNP, with all three Trp residues replaced by Tyr) retains near-normal kinetic properties. Studies with this construct established: (1) guanine bound to PNP adopts the N1H, 6-keto, N7H tautomer as its fluorescent form; (2) phosphate and guanine bind randomly to PNP; (3) ternary complex formation does not involve kinetically significant protein conformational changes (monitored by fluorescence); (4) Tyr88 hydroxyl is not ionized to phenolate when phosphate is bound; (5) the loop region (residues 243–266) near the purine base becomes highly ordered upon substrate/inhibitor binding. Site-directed mutagenesis (Trp→Tyr substitutions), kinetic analysis, fluorescence spectroscopy, 13C NMR, temperature-jump experiments, X-ray crystallography Biochemistry High 18269249
2013 19F-NMR and X-ray crystallography with site-specific 6-fluoro-tryptophan substitutions at His257 or His64 positions in human PNP revealed that the catalytic site loops coexist in multiple conformational states in the phosphate-bound enzyme, and these dynamic conformations become altered or reduced to single conformations upon binding of transition-state analogs or other catalytic site ligands. 19F-NMR with site-specific 6-fluoro-tryptophan labeling combined with X-ray crystallography of multiple complexes Chemistry & biology High 23438750
1997 PNP inhibition (CI-1000) combined with deoxyguanosine causes T-cell death via apoptosis mediated by caspase-3-like protease activation, as evidenced by PARP cleavage (85 kDa fragment), alpha-spectrin cleavage (120 kDa fragment), loss of intact caspase-3, and elevated caspase-3 fluorometric activity. A pan-caspase inhibitor and deoxycytidine (which prevents dGTP accumulation) both blocked cell death and all caspase-3 indicators. Cell viability assays, Western blotting for PARP and alpha-spectrin cleavage products, fluorometric caspase-3 activity assays, Hoechst nuclear staining, rescue experiments Immunopharmacology High 9403342
2017 A missense SNP (rs1049564) in human PNP causes reduced PNP mRNA and protein expression and decreased enzymatic activity even when protein levels are controlled (loss-of-function variant). Homozygous TT lymphoblastoid cells show a 2-fold increase in S-phase cell cycle block that is pharmacologically reversible by hypoxanthine and adenosine, supporting relative PNP deficiency as the cause. The TT genotype also increases type I IFN pathway activation in a dose-response manner. Lymphoblastoid cell lines with known genotypes, enzyme activity assays, flow cytometry cell cycle analysis, pharmacological rescue with hypoxanthine/adenosine, IFN-induced gene expression assays Arthritis & rheumatology (Hoboken, N.J.) Medium 28859258
2006 PNP fused to a protein transduction domain (PTD-PNP) rapidly enters PNP-deficient lymphocytes, increases intracellular enzyme activity for up to 96 hours, and is predominantly distributed in the cytoplasm (consistent with endogenous PNP localization). PTD-PNP corrected abnormal T-cell functions including mitogenic response and IL-2 secretion, confirming that PNP is an intracellular cytoplasmic enzyme essential for T-cell purine metabolism. Protein transduction into PNP-deficient lymphocytes, subcellular fractionation, enzyme activity assays, T-cell functional assays (proliferation, IL-2 secretion) Cellular immunology Medium 16930574
2021 In C. elegans, the PNP ortholog pnp-1 acts in intestinal epithelial cells as a negative regulator of the Intracellular Pathogen Response (IPR). Loss of pnp-1 increases resistance to both intracellular and extracellular pathogens. Metabolomics showed pnp-1 enzymatic activity (converting purine nucleosides to free bases) is conserved, and perturbations in purine metabolism are monitored as a host defense cue. Forward genetic screen, pnp-1 mutant analysis, metabolomics, pathogen resistance assays, IPR gene expression analysis PLoS pathogens Medium 33878133
2017 Human PNP is constitutively released from rat C6 glioma cells into the extracellular medium with similar molecular weight and enzymatic activity to the cytosolic enzyme. Selective activation of P2Y1 or A2A receptors increased extracellular PNP release. Hypoxia decreased released PNP levels (increasing extracellular nucleosides), while re-oxygenation enhanced PNP release, demonstrating that extracellular PNP contributes to purinergic system homeostasis. Cell culture medium analysis, enzyme activity assays, receptor agonist pharmacology, hypoxia/re-oxygenation experiments Journal of neurochemistry Medium 28251649
2007 Kinetic studies on human erythrocyte PNP showed that the dianionic form of inorganic phosphate (Pi) is the preferred cosubstrate over the monoanionic form, with enzyme efficiency three orders of magnitude higher at pH 8 than pH 5. Both human and E. coli PNP exhibit negative cooperativity in Pi binding (Hill coefficient <1), suggesting allosteric communication between active sites. Enzyme kinetics across pH 5–8, comparison of phosphate vs thiophosphate as cosubstrate, Hill coefficient analysis European biophysics journal : EBJ Medium 17639373
2001 E. coli PNP binds both the cationic and zwitterionic forms of N7-methylguanosine (m7Guo), with the zwitterion having 3-fold lower affinity. m7Guo binding to E. coli PNP exhibits negative cooperativity (Hill constant <1), in contrast to guanosine binding which is non-cooperative. The product N7-methylguanine is a competitive non-substrate inhibitor (Ki = 8 µM). Fluorescence quenching is a static process, and mean excited-state lifetime is unchanged upon ligand binding. Steady-state and time-resolved fluorescence spectroscopy, enzyme kinetics, fluorescence quenching analysis Biochimica et biophysica acta Medium 11341918
2000 E. coli PNP interacts with formycin A (FA) and its N-methyl analogues via fluorescence resonance energy transfer (FRET) from protein tyrosine residues to the FA base moiety. Complex formation with FA shifts the tautomeric equilibrium from the N1-H form to the N2-H form independently of phosphate. With m6FA in the presence of phosphate, an amino-to-imino tautomeric shift occurs with markedly increased affinity (Kd = 0.5 µM vs 46 µM without phosphate), demonstrating that phosphate binding modulates nucleoside binding affinity. Binding stoichiometry is one ligand per native enzyme hexamer. Steady-state and time-resolved fluorescence spectroscopy, excitation/emission/absorption spectral analysis, Stern-Volmer quenching analysis Biochimica et biophysica acta Medium 10606773
2011 miR-1 and miR-133a directly regulate PNP expression in prostate cancer cells, as demonstrated by genome-wide gene expression analysis and luciferase reporter assay. Silencing of PNP gene inhibited proliferation, migration, and invasion of PC3 and DU145 prostate cancer cells, identifying PNP as a functional oncogenic target of these tumor-suppressor miRNAs. miRNA restoration, genome-wide gene expression analysis, luciferase reporter assay (3'UTR targeting), siRNA-mediated PNP knockdown with proliferation/migration/invasion assays British journal of cancer Medium 22068816
2020 SAMHD1 (a dNTP hydrolase) prevents the accumulation of toxic dNTP levels during PNP inhibition, thereby protecting cancer cells from PNP inhibitor-induced cell death. Cancer cells lacking SAMHD1 are selectively killed by PNP inhibitors, establishing SAMHD1 as a resistance factor for PNP inhibitor therapy. Cell viability assays in SAMHD1-deficient vs proficient cell lines treated with PNP inhibitors Molecular & cellular oncology Low 33235905

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Crystal structure of an activated Akt/protein kinase B ternary complex with GSK3-peptide and AMP-PNP. Nature structural biology 444 12434148
2008 Modularly designed transition metal PNP and PCP pincer complexes based on aminophosphines: synthesis and catalytic applications. Accounts of chemical research 216 18211031
1988 Stabilization of discrete mRNA breakdown products in ams pnp rnb multiple mutants of Escherichia coli K-12. Journal of bacteriology 203 2459106
2011 Tumour suppressors miR-1 and miR-133a target the oncogenic function of purine nucleoside phosphorylase (PNP) in prostate cancer. British journal of cancer 176 22068816
2012 Structure of AMP-PNP-bound vitamin B12 transporter BtuCD-F. Nature 137 23000901
1987 Nucleotide sequence of the pnp gene of Escherichia coli encoding polynucleotide phosphorylase. Homology of the primary structure of the protein with the RNA-binding domain of ribosomal protein S1. The Journal of biological chemistry 102 2432069
1994 Roles of RNase E, RNase II and PNPase in the degradation of the rpsO transcripts of Escherichia coli: stabilizing function of RNase II and evidence for efficient degradation in an ams pnp rnb mutant. The EMBO journal 101 7519147
2001 PNPase autocontrols its expression by degrading a double-stranded structure in the pnp mRNA leader. The EMBO journal 90 11726520
1998 The psychrotrophic bacterium Yersinia enterocolitica requires expression of pnp, the gene for polynucleotide phosphorylase, for growth at low temperature (5 degrees C). Molecular microbiology 79 9632258
1990 Properties of purine nucleoside phosphorylase (PNP) of mammalian and bacterial origin. Zeitschrift fur Naturforschung. C, Journal of biosciences 79 2109978
1994 Localization of phosphoneuroprotein 14 (PNP 14) and its mRNA expression in rat brain determined by immunocytochemistry and in situ hybridization. Brain research. Molecular brain research 75 7877458
2014 Catalytic mechanisms of direct pyrrole synthesis via dehydrogenative coupling mediated by PNP-Ir or PNN-Ru pincer complexes: crucial role of proton-transfer shuttles in the PNP-Ir system. Journal of the American Chemical Society 71 24611673
2003 NMR chemical shift perturbation study of the N-terminal domain of Hsp90 upon binding of ADP, AMP-PNP, geldanamycin, and radicicol. Chembiochem : a European journal of chemical biology 69 12964162
2003 Mechanism of inhibition of T-acute lymphoblastic leukemia cells by PNP inhibitor--BCX-1777. International immunopharmacology 67 12781704
1999 Crystal structure of the purine nucleoside phosphorylase (PNP) from Cellulomonas sp. and its implication for the mechanism of trimeric PNPs. Journal of molecular biology 58 10600382
2010 Ruthenium complexes with cooperative PNP-pincer amine, amido, imine, and enamido ligands: facile ligand backbone functionalization processes. Inorganic chemistry 57 20486648
2003 Structural basis for inhibition of human PNP by immucillin-H. Biochemical and biophysical research communications 53 13679061
2014 Structure of AMP-PNP-bound BtuCD and mechanism of ATP-powered vitamin B12 transport by BtuCD-F. Nature structural & molecular biology 51 25402482
2021 The purine nucleoside phosphorylase pnp-1 regulates epithelial cell resistance to infection in C. elegans. PLoS pathogens 50 33878133
2005 Structure of human PNP complexed with ligands. Acta crystallographica. Section D, Biological crystallography 48 15983407
2003 Crystal structure of human PNP complexed with guanine. Biochemical and biophysical research communications 47 14680831
1984 Expression of the rpsO and pnp genes: structural analysis of a DNA fragment carrying their control regions. Nucleic acids research 47 6382163
1994 Nucleolytic inactivation and degradation of the RNase III processed pnp message encoding polynucleotide phosphorylase of Escherichia coli. Journal of molecular biology 46 7516438
2007 Crystal structure of the kinase domain of serum and glucocorticoid-regulated kinase 1 in complex with AMP PNP. Protein science : a publication of the Protein Society 44 17965184
2004 Crystal structures of Escherichia coli RecA in complex with MgADP and MnAMP-PNP. Biochemistry 43 15610008
1996 Structure of the R65Q mutant of yeast 3-phosphoglycerate kinase complexed with Mg-AMP-PNP and 3-phospho-D-glycerate. Biochemistry 43 8672447
2010 Discovery of new inhibitors of Schistosoma mansoni PNP by pharmacophore-based virtual screening. Journal of chemical information and modeling 42 20695479
1981 Cloning of E. coli pnp gene from an episome. Molecular & general genetics : MGG 40 6276682
2014 Final results of a multicenter phase II study of the purine nucleoside phosphorylase (PNP) inhibitor forodesine in patients with advanced cutaneous T-cell lymphomas (CTCL) (Mycosis fungoides and Sézary syndrome). Annals of oncology : official journal of the European Society for Medical Oncology 38 24948692
2001 Two novel mutations in a purine nucleoside phosphorylase (PNP)-deficient patient. Clinical genetics 38 11453975
2019 Thermodynamic Analysis of Metal-Ligand Cooperativity of PNP Ru Complexes: Implications for CO2 Hydrogenation to Methanol and Catalyst Inhibition. Journal of the American Chemical Society 36 31390860
2000 Formycin A and its N-methyl analogues, specific inhibitors of E. coli purine nucleoside phosphorylase (PNP): induced tautomeric shifts on binding to enzyme, and enzyme-->ligand fluorescence resonance energy transfer. Biochimica et biophysica acta 35 10606773
2018 Simultaneous p-nitrophenol and nitrogen removal in PNP wastewater treatment: Comparison of two integrated membrane-aerated bioreactor systems. Journal of hazardous materials 34 30308370
2015 Structures of the CDK12/CycK complex with AMP-PNP reveal a flexible C-terminal kinase extension important for ATP binding. Scientific reports 34 26597175
2004 Purine nucleoside phosphorylase deficiency (PNP-def) presenting with lymphopenia and developmental delay: successful correction with umbilical cord blood transplantation. The Journal of pediatrics 34 15520787
2007 Two distinct modes of processive kinesin movement in mixtures of ATP and AMP-PNP. The Journal of general physiology 33 17968024
2020 PLANT NATRIURETIC PEPTIDE A and Its Putative Receptor PNP-R2 Antagonize Salicylic Acid-Mediated Signaling and Cell Death. The Plant cell 32 32409317
2023 Versatile CO2 Hydrogenation-Dehydrogenation Catalysis with a Ru-PNP/Ionic Liquid System. Journal of the American Chemical Society 31 36867088
2005 PNP anticancer gene therapy. Current topics in medicinal chemistry 31 16305530
2003 The [(99m)Tc(N)(PNP)](2+) metal fragment: a technetium-nitrido synthon for use with biologically active molecules. The N-(2-methoxyphenyl)piperazyl-cysteine analogues as examples. Bioconjugate chemistry 31 14624640
1987 Tn5 insertion in the polynucleotide phosphorylase (pnp) gene in Escherichia coli increases susceptibility to antibiotics. Journal of bacteriology 31 3029034
2015 CsrA Participates in a PNPase Autoregulatory Mechanism by Selectively Repressing Translation of pnp Transcripts That Have Been Previously Processed by RNase III and PNPase. Journal of bacteriology 29 26438818
2008 Molecular modeling and dynamics simulations of PNP from Streptococcus agalactiae. Bioorganic & medicinal chemistry 29 18381241
1990 Escherichia coli glyA mRNA decay: the role of 3' secondary structure and the effects of the pnp and rnb mutations. Molecular & general genetics : MGG 29 1691434
2012 Involvement of pnp in survival of UV radiation in Escherichia coli K-12. Microbiology (Reading, England) 28 22322961
2004 Structural bioinformatics study of PNP from Schistosoma mansoni. Biochemical and biophysical research communications 28 15313179
2005 Crystal structure of human PNP complexed with hypoxanthine and sulfate ion. Biochemical and biophysical research communications 27 15582582
2005 The absB gene encodes a double strand-specific endoribonuclease that cleaves the read-through transcript of the rpsO-pnp operon in Streptomyces coelicolor. The Journal of biological chemistry 27 16076842
1997 Inhibition of ecto-ATPase by the P2 purinoceptor agonists, ATPgammaS, alpha,beta-methylene-ATP, and AMP-PNP, in endothelial cells. Biochemical and biophysical research communications 27 9144554
2008 Tryptophan-free human PNP reveals catalytic site interactions. Biochemistry 25 18269249
2003 Overexpression of the polynucleotide phosphorylase gene (pnp) of Streptomyces antibioticus affects mRNA stability and poly(A) tail length but not ppGpp levels. Microbiology (Reading, England) 25 12904557
2012 Branching of the p-nitrophenol (PNP) degradation pathway in burkholderia sp. Strain SJ98: Evidences from genetic characterization of PNP gene cluster. AMB Express 24 22681853
2005 Antibiotic-mediated chemoprotection enhances adaptation of E. coli PNP for herpes simplex virus-based glioma therapy. Human gene therapy 24 15812229
1985 Attenuation and processing of RNA from the rpsO-pnp transcription unit of Escherichia coli. Nucleic acids research 24 2414737
2017 Lupus-Associated Functional Polymorphism in PNP Causes Cell Cycle Abnormalities and Interferon Pathway Activation in Human Immune Cells. Arthritis & rheumatology (Hoboken, N.J.) 22 28859258
2006 Intracellular delivery of purine nucleoside phosphorylase (PNP) fused to protein transduction domain corrects PNP deficiency in vitro. Cellular immunology 22 16930574
1996 Distribution of phosphoneuroprotein 14 (PNP 14) in vertebrates: its levels as determined by enzyme immunoassay. Brain research 22 9001721
1993 Differences in the interaction of p21c-Ha-ras-GMP-PNP with full-length neurofibromin and GTPase-activating protein. Oncogene 22 8437847
2019 Square Planar Cobalt(II) Hydride versus T-Shaped Cobalt(I): Structural Characterization and Dihydrogen Activation with PNP-Cobalt Pincer Complexes. Inorganic chemistry 21 31002499
2016 Chemoenzymatic synthesis of para-nitrophenol (pNP)-tagged α2-8-sialosides and high-throughput substrate specificity studies of α2-8-sialidases. Organic & biomolecular chemistry 21 27924345
1996 Two novel missense and frameshift mutations in exons 5 and 6 of the purine nucleoside phosphorylase (PNP) gene in a severe combined immunodeficiency (SCID) patient. Human genetics 21 8931706
2002 Evidence that the putative alpha-glucosidase of Thermotoga maritima MSB8 is a pNP alpha-D-glucuronopyranoside hydrolyzing alpha-glucuronidase. FEBS letters 20 12062428
2004 Organization and expression of the polynucleotide phosphorylase gene (pnp) of Streptomyces: Processing of pnp transcripts in Streptomyces antibioticus. Journal of bacteriology 19 15126478
2020 Ru0 or RuII: A Study on Stabilizing the "Activated" Form of Ru-PNP Complexes with Additional Phosphine Ligands in Alcohol Dehydrogenation and Ester Hydrogenation. Inorganic chemistry 18 32196320
2018 An ultrasonic nanobubble-mediated PNP/fludarabine suicide gene system: A new approach for the treatment of hepatocellular carcinoma. PloS one 18 29718963
2007 Avidin-biotin system: a small library of cysteine biotinylated derivatives designed for the [99mTc(N)(PNP)]2+ metal fragment. Nuclear medicine and biology 16 17591551
1989 Characterization of mitotic motors by their relative sensitivity to AMP-PNP. Journal of cell science 16 2698890
1976 Catecholamine-sensitive adenylate cyclase of human fat cell ghosts. Characteristics of the GMP(PNP)-liganded state. Clinica chimica acta; international journal of clinical chemistry 16 11915
2011 RNase III-dependent expression of the rpsO-pnp operon of Streptomyces coelicolor. Journal of bacteriology 15 21742867
2007 Synthesis and biological evaluation of 9-deazaguanine derivatives connected by a linker to difluoromethylene phosphonic acid as multi-substrate analogue inhibitors of PNP. Bioorganic & medicinal chemistry letters 15 17544667
2013 Catalytic site conformations in human PNP by 19F-NMR and crystallography. Chemistry & biology 14 23438750
2020 PNP inhibitors selectively kill cancer cells lacking SAMHD1. Molecular & cellular oncology 13 33235905
2017 Evidence for purine nucleoside phosphorylase (PNP) release from rat C6 glioma cells. Journal of neurochemistry 13 28251649
2008 Overexpression, purification and characterization of functional calf purine nucleoside phosphorylase (PNP). Protein expression and purification 13 18585465
2006 Drug evaluation: forodesine - PNP inhibitor for the treatment of leukemia, lymphoma and solid tumor. IDrugs : the investigational drugs journal 13 17016779
1998 7-Deazapurine 2'-deoxyribofuranosides are noncleavable competitive inhibitors of Escherichia coli purine nucleoside phosphorylase (PNP). Acta biochimica Polonica 13 9918502
1976 Further studies on the isolation and properties of polyriboadenylate polymerase from Escherichia coli PR7 (RNase I-, pnp). The Journal of biological chemistry 13 789366
2017 4-Nitrophenol (PNP) inhibits the expression of estrogen receptor β and disrupts steroidogenesis during the ovarian development in female rats. Environmental pollution (Barking, Essex : 1987) 12 28570923
1995 Correction of proliferative responses in purine nucleoside phosphorylase (PNP)-deficient T lymphocytes by retroviral-mediated PNP gene transfer and expression. Journal of immunology (Baltimore, Md. : 1950) 12 7876563
2019 The Broad Clinical Spectrum and Transplant Results of PNP Deficiency. Journal of clinical immunology 11 31707514
2009 Backbone NMR resonance assignment of the catalytic subunit of cAMP-dependent protein kinase A in complex with AMP-PNP. Biomolecular NMR assignments 11 19636960
2007 The [Tc(N)(PNP)]2+ metal fragment labeled cholecystokinin-8 (CCK8) peptide for CCK-2 receptors imaging: in vitro and in vivo studies. Journal of peptide science : an official publication of the European Peptide Society 11 17269133
2007 Role of ionization of the phosphate cosubstrate on phosphorolysis by purine nucleoside phosphorylase (PNP) of bacterial (E. coli) and mammalian (human) origin. European biophysics journal : EBJ 11 17639373
1995 Influence of ADP, AMP-PNP and of depletion of nucleotides on the structural properties of F1ATPase: a Fourier transform infrared spectroscopic study. FEBS letters 11 7589453
1990 Inhibition of the enzyme purine nucleoside phosphorylase (PNP) reduces refractoriness to transfused platelets in a dog model. British journal of haematology 11 2119794
2021 Effect of Pincer Methylation on the Selectivity and Activity in (PNP)Cobalt-Catalyzed C(sp2)-H Borylation. Organometallics 10 34898806
2019 In vitro effects of PNP and PNMC on apoptosis and proliferation in the hen ovarian stroma and prehierarchal follicles. Acta histochemica 10 31708232
1992 Processing in the 5' region of the pnp transcript facilitates the site-specific endonucleolytic cleavages of mRNA. Nucleic acids research 10 1371867
1992 The biochemistry and pharmacology of PD 116124 (8-amino-2'-nordeoxyguanosine), an inhibitor of purine nucleoside phosphorylase (PNP). The Journal of pharmacology and experimental therapeutics 10 1530976
1981 Purine nucleoside phosphorylase (PNP) and adenosine deaminase (ADA) activities examined cytochemically in unfixed lymphocytes of patients with lymphoproliferative disorders. Blood 10 6794677
2023 Detoxification of p-nitrophenol (PNP) using Enterococcus gallinarum JT-02 isolated from animal farm waste sludge. Environmental research 9 37263467
2022 Rare-Earth-Metal Complexes Bearing an Iminodibenzyl-PNP Pincer Ligand: Synthesis and Reactivity toward 3,4-Selective Polymerization of 1,3-Dienes. Inorganic chemistry 9 34990130
2021 Early Diagnosis and Treatment of Purine Nucleoside Phosphorylase (PNP) Deficiency through TREC-Based Newborn Screening. International journal of neonatal screening 9 34698070
2018 [99mTc][Tc(N)(DASD)(PNP n)]+ (DASD = 1,4-Dioxa-8-azaspiro[4,5]decandithiocarbamate, PNP n = Bisphosphinoamine) for Myocardial Imaging: Synthesis, Pharmacological and Pharmacokinetic Studies. Journal of medicinal chemistry 9 30495949
2014 Ionic size effects to molecular solvation energy and to ion current across a channel resulted from the nonuniform size-modified PNP equations. The Journal of chemical physics 9 24811620
2011 Purine nucleoside phosphorylase deficiency with a novel PNP gene mutation: a first case report from India. BMJ case reports 9 22669887
2005 Bone mass and strength: phenotypic and genetic relationship to alcohol preference in P/NP and HAD/LAD rats. Alcoholism, clinical and experimental research 9 16269906
2001 Interaction of Escherichia coli purine nucleoside phosphorylase (PNP) with the cationic and zwitterionic forms of the fluorescent substrate N(7)-methylguanosine. Biochimica et biophysica acta 9 11341918
2000 Hereditary persistent right oviduct in the chicken PNP/DO line. Poultry science 8 10947174
1997 A purine nucleoside phosphorylase (PNP) inhibitor induces apoptosis via caspase-3-like protease activity in MOLT-4 T cells. Immunopharmacology 8 9403342

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