PNP (Purine Nucleoside Phosphorylase)

2018-03-01 Rafig Gurbanov , Sinem Tunçer Affiliation

Identity

HGNC

PNP

LOCATION

14q11.2

IMAGE

LEGEND

Figure 1. Genomic location of PNP (Chromosome 14 - NC_000014.9 Reference GRCh38.p7 Primary Assembly)

LOCUSID

4860

ALIAS

NP,PRO1837,PUNP

Abstract

The purine nucleoside phosphorylase gene (PNP) encodes an enzyme which reversibly catalyzes the phosphorolysis of purine nucleosides. PNP is ubiquitously expressed in mammalian cells and tissues. PNP mutations cause nucleoside phosphorylase deficiency which result in defective T cell mediated immunity but can also affect B cell immunity and antibody responses.

DNA/RNA

Note

The PNP gene is 7,716 bp long (according to UCSC, GRCh38/hg38), located on the plus strandand spans 6 exons (NCBI Homo sapiens Annotation Release 108).

Transcription

The gene has 8 transcripts (Table 1)
Table 1. Transcripts of human PNP gene (Ensemble, GRCh38.p10).

Name	Transcript ID	bp	Protein (aa)	Biotype
PNP-201	ENST00000361505.9	1509	289	Protein coding
PNP-203	ENST00000553591.1	770	221	Protein coding
PNP-202	ENST00000553418.5	557	93	Protein coding
PNP-205	ENST00000554065.1	554	61	Protein coding
PNP-207	ENST00000556754.1	2573		Retained intron
PNP-204	ENST00000554056.5	1635		Retained intron
PNP-206	ENST00000556293.5	1023		Retained intron
PNP-208	ENST00000557229.5	992		Retained intron

Pseudogene

A pseudogene has been identified on chromosome 2 (NCBI Homo sapiens Annotation Release 108).

Proteins

Note

PNP encodes purine nucleoside phosphorylase (EC 2.4.2.1) (NCBI Homo sapiens Annotation Release 108). Mammalian PNPs are homotrimers with a monomeric molecular mass of about 31 kDa, each with a substrate-binding site (Figure 2) (Ting et al., 2004; Aust et al., 1992).

Figure 2. Structure of human purine nucleoside phosphorylase. Structure of human PNP determined using X-ray diffraction (PDB ID: 3BGS) (Rinaldo-Matthis et al., 2008).

Expression

PNP is ubiquitously expressed in human cells and tissues, but the highest activity is found in the peripheral red blood cells, blood granulocytes and lymphoid tissue (Roberts et al., 2004).

Localisation

PNP is present in both the cytosol and the mitochondria (Roberts et al., 2004).

Figure 3. Enzymatic pathways involved in the degradation of purine nucleosides. Thermodynamically, the equilibrium of the reaction is shifted in favor of nucleoside synthesis. However, phosphorolysis is highly favored over nucleoside synthesis, due to coupling with two additional enzymatic reactions: (1) oxidation and (2) phosphoribosylation of the liberated purine bases by xanthine oxidase (Xox) and hypoxanthine-guanine phosphoribosyltransferase (HGPRT), respectively (modified from Giuliani et al., 2016).

Function

The PNP catalyzes the reversible phosphorolysis of purine nucleosides (primarily inosine and guanosine in humans) to generate the corresponding purine base and ribose 1-phosphate inosine in the presence of inorganic orthophosphate (Pi) (Jonsson et al., 1992; Furihata et al., 2014). PNP is a ubiquitous enzyme of purine metabolism that functions in the salvage pathway, thus enabling the cells to synthesize purine nucleotides from purine bases by avoiding the ex-novo synthesis which is energetically expensive (Figure 3). Under normal conditions, phosphorolysis is favored due to the coupling of the PNP reaction with either purine base oxidation by xanthine oxidase or purine base phosphoribosylation by hypoxanthine-guanine phosphoribosyl transferase (HGPRT). On the other hand, nucleoside synthesis is thermodynamically favored over phosphorolysis (Erion et al., 1997; Bzowska et al., 2000).
PNP activity is crucial for cell survival and function. PNP deficiency results in the accumulation of its substrates: inosine, deoxyinosine, guanosine, and deoxyguanosine. Increased phosphorylation of deoxyguanosine leads to dGTP accumulation, a potent feedback inhibitor of human ribonucleotide reductase. dGTP accumulation can also interfere with DNA synthesis or repair directly (Arpaia et al., 2000; Ghodke-Puranik et al., 2017) (Figure 4). Abnormal activity of the enzyme is associated with different pathologies (Giuliani et al., 2016).

Figure 4. PNP in the degradation and salvage pathways of purine nucleosides. Phosphorolysis of the products of the ADA reaction, inosine and deoxyinosine, is catalyzed by PNP to yield hypoxanthine and ribose-1-phosphate. Of the four PNP substrates, only deoxyguanosine is phosphorylated by the mitochondrial deoxyguanosine kinase (dGK). Further phosphorylation of dGMP results in the accumulation of dGTP, which interferes with DNA synthesis or DNA repair directly or inhibits ribonucleotide reductase activity. The PNP product guanine is salvaged back to the guanine nucleotide pools by HGPRT activity (modified from Arpaia et al., 2000).

Homology

PNP enzyme has been isolated isolated from different species, including bacteria, protozoa, rodents, and mammals. A high degree of homology is found between these PNP enzymes, with human and bovine and murine PNPs demonstrating more than 87% and 84% homology, respectively (Ochs et al., 2013) (Figure 5).

Figure 5. Pairwise alignment of PNP gene and PNP protein sequences (in distance from human) (HomoloGene, NCBI).

Mutations

Note

PNP deficiency is caused by PNP gene mutations. As mentioned before, PNP contains six exons. Exon skipping, missense, and frameshift mutations in these six exons have been found to cause PNP deficiency, and the most frequent mutations are the substitution of A to C or A to G at cDNA position 58 or 234, respectively (Brodszki et al., 2015). Up-to-date and comprehensive list of PNP associated mutations was given in Table 2. Furthermore, it should be also considered that PNP polymorphisms might be associated with variability in the clinical presentation and course of affected patients (Moallem et al., 2002).
Table 2. Purine nucleoside phosphorylase (PNP) deficiency related mutations.

#	Location	Mutation	Protein	Reference
[1]	Exon 2	c.59A>C	p.20H>P	Yeates et al., 2017
[2]	Exon 2	c.70C>T	p.Arg24X	Walker et al., 2011
[3]	Exon 2	c.172C>T	p.Arg57X	Walker et al., 2011
[4]	Exon 2	c.181G>T	p.Tyr5AlafsX28	Walker et al., 2011
[5]	Exon 3	c.199C>T	p.Arg67X	Walker et al., 2011
[6]	Exon 3	c.212G>A	p.71Gly>Glu	Walker et al., 2011
[7]	Exon 3	c.257A>G	p.86His>Arg	Walker et al., 2011
[8]	Exon 3	c.265G>A	p.89Glu>Lys	Walker et al., 2011
[9]	Exon 4	c.349G>A	p.117Ala>Thr	Grunebaum et al., 2004
[10]	Exon 4	c.383A>G	p.128Asp>Gly	Walker et al., 2011
[11]	Exon 4	c.385 387delATC	p.Ile129del	Walker et al., 2011
[12]	Exon 4	c.437C>T	p.146Pro>Leu	Alangari et al., 2009
[13]	Exon 5	c.467G>C	p.156Gly>Ala	Moallem et al., 2002
[14]	Exon 5	c.475T>G	p.159Phe>Val	Walker et al., 2011
[15]	Exon 5	c.487T>C	p.163Ser>Pro	Al-Saud et al., 2009
[16]	Exon 5	c.520G>C	p.174Ala>Pro	Walker et al., 2011
[17]	Exon 5	c.569G>T	p.190Gly>Val	Walker et al., 2011
[18]	Exon 5	c.575A>G	p.192Tyr>Cys	Walker et al., 2011
[19]	Exon 6	c.700C>G	p.Arg234X	Walker et al., 2011
[20]	Exon 6	c.701G>C	p.234Arg>Pro	Walker et al., 2011
[21]	Exon 6	c.729C>G	p.Asn243Lys	Brodszki et al., 2015
[22]	Exon 6	c.730delA	p.Lys244ArgfsX17	Walker et al., 2011
[23]	Exon 6	.746A>C	p.Tyr249Cys	Brodszki et al., 2015
[25]	Exon 6	c.770A>G	p.257His>Arg	Walker et al., 2011
[26]	Intron 3	c.285+1G>A	p.Val61GlyfsX30	Walker et al., 2011

Implicated in

Top note

Associated Pathologies
When PNP is defective, dGTP accumulation inhibits DNA replication and mitochondrial DNA repair which cause increased sensitivity of T lymphocytes to DNA damage and apoptosis during thymus selection. In addition, the lack of DNA replication is critical especially in the immune system: PNP deficiency leads to S-phase block in 7-11% of circulating lymphocytes. Mutations leading to PNP deficiency result in an autosomal recessive disorder known as severe combined immune deficiency (SCID) characterized by a profound deficiency in T cell function with variable B cell involvement. PNP deficiency is a very rare autosomal recessive condition, accounting for approximately 4% of all SCID cases (Madkaikar et al., 2011; Ghodke-Puranik et al., 2017). Small hypoplastic thymus, reduced T lymphocytes in peripheral blood, abnormal response of T lymphocytes to stimulation, and enlarged spleen are found in most PNP-deficient patients (Toro and Grunebaum, 2006). Lymphopenia, reduced serum uric acid, and abnormal PNP enzymatic activity assist in the diagnosis of PNP deficiency. Patients with SCID lack virtually all immune protection from foreign invaders such as bacteria, viruses, and fungi, therefore they are prone to repeated and persistent infections that can be very detrimental and life threatening. About two-thirds of individuals with PNP deficiency have neurological problems, including hypertonia, spasticity, tremors, ataxia, retarded motor development, behavioral difficulties, and varying degrees of mental retardation. People with PNP deficiency are also at increased risk of developing autoimmune disorders (autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura-ITP, autoimmune neutropenia, thyroiditis, and lupus). Infants with SCID typically grow much more slowly than healthy children and experience pneumonia, chronic diarrhea, and widespread skin rashes. Without successful treatment to restore immune function, children with SCID usually live only into early childhood. Lymphoma and lymphosarcoma have also been reported in children with PNP immunodeficiency (Ghodke-Puranik et al., 2017; Arpaia et al., 2000).
On the other hand, PNP levels are significantly upregulated in several tumor cells (Figure 6). In comparison with healthy individuals, PNP activity was shown to be higher in lymphocytes of patients suffering from bronchogenic carcinoma (Gierek et al., 1987; Rendeková et al., 1983). Sanfilippo et al. claimed a relationship between tissue PNP and tumor invasiveness in human colon carcinoma (Sanfilippo et al., 1994). Furthermore, Roberts et al. showed that plasma PNP activity was higher also in patients with breast, gastric, colon, lung and ovarian cancers and lymphoma (Roberts et al., 2004). From the biomarker perspective, Vareed et al. found that PNP levels were higher in sera from pancreatic adenocarcinoma patients and levels of PNP-regulated metabolites in serum, guanosine and adenosine, were suitable to determine pancreatic adenocarcinoma and distinguish pancreatic adenocarcinoma from benign tumors (Vareed et al., 2011). Plasma PNP activity was also higher in patients with asthma than in either healthy subjects or patients with gout (Yamamoto et al., 1995). However, a low level of PNP activity was found in mononuclear cells from patients with acute myeloid and lymphoblastic leukemia and with chronic lymphocytic leukemia (Morisaki et al., 1986).
Treatment
Bone marrow transplantation in PNP deficiency has been attempted with variable degree of success. However, HLA-matched donors are not readily available, and transplants using HLA incompatible donors are frequently result in procedure-related morbidity, graft-versus-host disease or graft loss (Liao et al., 2008). Myers et al. suggested umbilical cord blood, a readily available and pathogen-free source of stem cells, transplantation as a treatment option for patients with PNP deficiency who do not have a HLA-matched donor (Myers et al., 2004).
Gene therapy with autologous cells, either total bone marrow (BM) or hematopoietic stem cells (HSCs) isolated from the BM, transduced with the normal gene sequence that can express the missing protein represents an attractive option for inherited hematological and immunological defects, including PNP deficiency (Liao et al., 2008). In in vitro, Foresman et al. showed that retroviral-mediated PNP gene transfer and expression correct the metabolic defects caused by PNP deficiency in murine lymphoid cells (Foresman et al., 1992). In PNP -/- mouse model, PNP deficiency was corrected by transplanting BM cells which have been transduced with lentiviral vectors containing the human PNP gene (lentiPNP) (Liao et al., 2008). However, 12 weeks after transplant, benefit of lentiPNP transduced cells decreased, which indicates that an improved gene expression strategy is required to afford a successful gene therapy for PNP deficiency (Liao et al., 2008). Indeed, PNP enzyme replacement therapy has been evaluated in PNP -/- mice by administration of PNP fused trans-activator of transcription (TAT) protein (TAT-PNP). TAT induced rapid and efficient delivery of active PNP into many tissues, including the brain, and TAT-PNP remained effective over 24 weeks post-treatment, and corrected metabolic abnormalities and immunodeficiency, and extended survival (Toro and Grunebaum, 2006). Similarly, PNP fused with protein transduction domain (PTD) from TAT protein was found to rapidly enter PNP deficient lymphocytes and increase intracellular enzyme activity for 96 h, and correct abnormal functions of PNP deficient lymphocytes including their response to stimulation and IL-2 secretion, in vitro (Toro et al., 2006). These results show that fusion protein approach for PNP deficiency is an attractive and promising method for intracellular delivery of PNP.
Since PNP deficiency results in selective cellular immunodeficiency, PNP inhibitors are considered to be potentially effective suppressors of T cell proliferative diseases, such as T cell lymphoma and T cell related autoimmune diseases, and may also be useful for the suppression of the graft-versus-host reaction (Ting et al., 2004). In addition, PNP inhibitors have shown to be promising based on their ability to potentiate the in vivo activity of antiviral and anticancer drugs (Erion et al., 1997). As an enzyme prodrug model, Krais et al. generated a fusion protein called as PNP-AV which is composed of E. coli PNP and human annexin V (AV). AV binds to phosphatidylserine (PS) expressed externally on tumor cells and endothelial cells of tumor vasculature, but not normal vascular endothelial cells. In in vitro, the recombinant fusion protein of PNP-AV was shown to bind and kill breast cancer and endothelial cells when used in the enzyme prodrug therapy with fludarabine. Krais et al. proposed that this approach allows for systemic administration of the fusion protein, with targeted accumulation of PNP in the tumor. After clearance of PNP-AV from the bloodstream, fludarabine, the substrate of E. coli PNP, can be administered systemically, so that 2-fluoroadenine is generated at the surface of the endothelial cells lining the tumor vasculature. This freely diffusible molecule is able to enter the cell and inhibit protein, RNA, and DNA synthesis in endothelial cell of tumor blood vessel. Since fludarabine is not a substrate of human PNP, the conversion of fludarabine to 2-fluoroadenine will not occur in normal tissue. Therefore, authors suggested that this strategy can be successful as a targeted therapy for breast cancer (Krais et al., 2013). More recently, phase I dose-escalating trial of E. coli PNP-fludarabine treatment was demonstrated to be safe and effective in head and neck squamous cell carcinoma, adenoid cystic carcinoma and melanoma. Successful regression of tumors without significant toxicity was shown in this first-in-human study of an effective prodrug activation strategy using E. coli PNP (Rosenthal et al., 2015).

Figure 6. PNP expression in primary tumors. Normalized gene expression data of RNASeqV2 which was extracted from TCGA using R package TCGA-Assembler (t test, adjusted p

Entity name

Lymphoma, Bronchogenic carcinoma, Colon carcinoma, Breast cancer, Gastric cancer, Lung cancer, Ovarian cancer, Pancreatic adenocarcinoma

Note

PNP activity was found higher in patients with indicated cancer types compared to control groups (Roberts et al., 2004; Rendeková et al., 1983; Sanfilippo et al., 1994; Vareed et al., 2011).

Entity name

Acute myeloid leukemia, Lymphoblastic leukemia, Chronic lymphocytic leukemia

Note

A low level of PNP activity was found in mononuclear cells from patients with acute myeloid and lymphoblastic leukemia and with chronic lymphocytic leukemia (Morisaki et al., 1986).

Entity name

Severe Combined Immune Deficiency (SCID)

Note

PNP deficiency is an autosomal recessive enzyme disorder, engaged in four percent of SCID cases in humans (Pannicke et al., 1996).

Entity name

Asthma

Note

PNP activity was higher in patients with asthma than in either healthy subjects or patients with gout (Yamamoto et al., 1995).

Bibliography

Pubmed ID	Last Year	Title	Authors
19733163	2009	A novel mutation in purine nucleoside phosphorylase in a child with normal uric acid levels.	Al-Saud B et al
10859343	2000	Mitochondrial basis for immune deficiency. Evidence from purine nucleoside phosphorylase-deficient mice.	Arpaia E et al
1384322	1992	Molecular analysis of mutations in a patient with purine nucleoside phosphorylase deficiency.	Aust MR et al
11337031	2000	Purine nucleoside phosphorylases: properties, functions, and clinical aspects.	Bzowska A et al
4582029	1972	[A congenital hyperplasia of Bowman's membrane].	Daicker B et al
9305962	1997	Purine nucleoside phosphorylase. 1. Structure-function studies.	Erion MD et al
1482702	1992	Correction of purine nucleoside phosphorylase deficiency by retroviral-mediated gene transfer in mouse S49 T cell lymphoma: a model for gene therapy of T cell immunodeficiency.	Foresman MD et al
24107682	2014	Functional analysis of purine nucleoside phosphorylase as a key enzyme in ribavirin metabolism.	Furihata T et al
28859258	2017	Lupus-Associated Functional Polymorphism in PNP Causes Cell Cycle Abnormalities and Interferon Pathway Activation in Human Immune Cells.	Ghodke-Puranik Y et al
3130041	1987	Adenosine deaminase and purine phosphorylase activities in lymphocytes and red blood cells of patients with carcinoma of the larynx.	Gierek T et al
26720700	2016	Development of a new HPLC method using fluorescence detection without derivatization for determining purine nucleoside phosphorylase activity in human plasma.	Giuliani P et al
15571269	2004	Novel mutations and hot-spots in patients with purine nucleoside phosphorylase deficiency.	Grunebaum E et al
1620616	1992	Intron requirement for expression of the human purine nucleoside phosphorylase gene.	Jonsson JJ et al
24098491	2013	Purine nucleoside phosphorylase targeted by annexin v to breast cancer vasculature for enzyme prodrug therapy.	Krais JJ et al
18924118	2008	Lentivirus gene therapy for purine nucleoside phosphorylase deficiency.	Liao P et al
22669887	2011	Purine nucleoside phosphorylase deficiency with a novel PNP gene mutation: a first case report from India.	Madkaikar MR et al
12483996	2002	Purine nucleoside phosphorylase deficiency: a new case report and identification of two novel mutations (Gly156A1a and Val217Ile), only one of which (Gly156A1a) is deleterious.	Moallem HJ et al
3094366	1986	Characterization of purine nucleoside phosphorylase in leukemia.	Morisaki T et al
8931706	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.	Pannicke U et al
6405288	1983	Adenosine deaminase and purine nucleoside phosphorylase activities in peripheral blood cells of patients with neoplastic diseases. I. Bronchogenic carcinoma.	Rendeková V et al
18154341	2008	L-Enantiomers of transition state analogue inhibitors bound to human purine nucleoside phosphorylase.	Rinaldo-Matthis A et al
15149878	2004	Plasma purine nucleoside phosphorylase in cancer patients.	Roberts EL et al
25899782	2015	Phase I dose-escalating trial of Escherichia coli purine nucleoside phosphorylase and fludarabine gene therapy for advanced solid tumors.	Rosenthal EL et al
7796389	1994	Relationship between the levels of purine salvage pathway enzymes and clinical/biological aggressiveness of human colon carcinoma.	Sanfilippo O et al
15448350	2004	Identification and characterization of a novel gene of grouper iridovirus encoding a purine nucleoside phosphorylase.	Ting JW et al
16964310	2006	TAT-mediated intracellular delivery of purine nucleoside phosphorylase corrects its deficiency in mice.	Toro A et al
16930574	2006	Intracellular delivery of purine nucleoside phosphorylase (PNP) fused to protein transduction domain corrects PNP deficiency in vitro.	Toro A et al
2841460	1988	Association of human papillomavirus with vulvodynia and the vulvar vestibulitis syndrome.	Turner ML et al
21448452	2011	Metabolites of purine nucleoside phosphorylase (NP) in serum have the potential to delineate pancreatic adenocarcinoma.	Vareed SK et al
22132981	2011	Purine nucleoside phosphorylase deficiency: a mutation update.	Walker PL et al
7668372	1995	Determination of plasma purine nucleoside phosphorylase activity by high-performance liquid chromatography.	Yamamoto T et al
28674683	2017	Infusion of Sibling Marrow in a Patient with Purine Nucleoside Phosphorylase Deficiency Leads to Split Mixed Donor Chimerism and Normal Immunity.	Yeates L et al

Other Information

Locus ID:

NCBI: 4860
MIM: 164050
HGNC: 7892
Ensembl: ENSG00000198805

Variants:

dbSNP: 4860
ClinVar: 4860
TCGA: ENSG00000198805
COSMIC: PNP

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000198805	ENST00000361505	P00491
ENSG00000198805	ENST00000361505	V9HWH6
ENSG00000198805	ENST00000553418	G3V2H3
ENSG00000198805	ENST00000553591	G3V5M2
ENSG00000198805	ENST00000554065	G3V393

Expression (GTEx)

100

150

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
Purine metabolism	KEGG	ko00230
Pyrimidine metabolism	KEGG	ko00240
Nicotinate and nicotinamide metabolism	KEGG	ko00760
Purine metabolism	KEGG	hsa00230
Pyrimidine metabolism	KEGG	hsa00240
Nicotinate and nicotinamide metabolism	KEGG	hsa00760
Metabolic pathways	KEGG	hsa01100
Immune System	REACTOME	R-HSA-168256
Innate Immune System	REACTOME	R-HSA-168249
Metabolism	REACTOME	R-HSA-1430728
Metabolism of nucleotides	REACTOME	R-HSA-15869
Purine metabolism	REACTOME	R-HSA-73847
Purine salvage	REACTOME	R-HSA-74217
Purine catabolism	REACTOME	R-HSA-74259
Neutrophil degranulation	REACTOME	R-HSA-6798695

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
18946041	2008	Atomic detail of chemical transformation at the transition state of an enzymatic reaction.	51
24792412	2014	AS3MT, GSTO, and PNP polymorphisms: impact on arsenic methylation and implications for disease susceptibility.	33
19425594	2009	Altered enthalpy-entropy compensation in picomolar transition state analogues of human purine nucleoside phosphorylase.	24
18281957	2008	Remote mutations alter transition-state structure of human purine nucleoside phosphorylase.	22
25338677	2015	Genetic analysis of the pathogenic molecular sub-phenotype interferon-alpha identifies multiple novel loci involved in systemic lupus erythematosus.	22
25625196	2015	The ligand binding mechanism to purine nucleoside phosphorylase elucidated via molecular dynamics and machine learning.	20
18281956	2008	Altered thermodynamics from remote mutations altering human toward bovine purine nucleoside phosphorylase.	18
20108972	2010	Conformational states of human purine nucleoside phosphorylase at rest, at work, and with transition state analogues.	13
19191546	2009	Loop-tryptophan human purine nucleoside phosphorylase reveals submillisecond protein dynamics.	12
14706628	2004	Structures of human purine nucleoside phosphorylase complexed with inosine and ddI.	11

Citation

Rafig Gurbanov ; Sinem Tunçer

PNP (Purine Nucleoside Phosphorylase)

Atlas Genet Cytogenet Oncol Haematol. 2018-03-01

Online version: http://atlasgeneticsoncology.org/gene/46893/pnp-(purine-nucleoside-phosphorylase)