Purine nucleoside phosphorylase

Not to be confused with polynucleotide phosphorylase.

purine-nucleoside phosphorylase
purine-nucleoside phosphorylase. PDB 1rct.
Identifiers
EC number	2.4.2.1
CAS number	9030-21-1
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / EGO
Search PMC articles PubMed articles NCBI proteins

Purine nucleoside phosphorylase
PDB rendering based on 1m73.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1M73, 1PF7, 1PWY, 1RCT, 1RFG, 1RR6, 1RSZ, 1RT9, 1ULA, 1ULB, 1V2H, 1V3Q, 1V41, 1V45, 1YRY, 2A0W, 2A0X, 2A0Y, 2OC4, 2OC9, 2ON6, 2Q7O, 3BGS, 3D1V, 3GB9, 3GGS, 3INY, 3K8O, 3K8Q, 3PHB, 4EAR, 4EB8, 4ECE, 4GKA
Identifiers
Symbols	PNP; NP; PRO1837; PUNP
External IDs	OMIM: 164050 MGI: 97365 HomoloGene: 227 ChEMBL: 4338 GeneCards: PNP Gene
EC number	2.4.2.1
Gene Ontology Molecular function • nucleoside binding • purine nucleobase binding • purine-nucleoside phosphorylase activity • drug binding • phosphate ion binding Cellular component • intracellular • cytoplasm • cytosol • cytoskeleton Biological process • nucleobase-containing compound metabolic process • purine nucleobase metabolic process • inosine catabolic process • purine nucleotide catabolic process • nicotinamide riboside catabolic process • immune response • NAD biosynthesis via nicotinamide riboside salvage pathway • urate biosynthetic process • positive regulation of T cell proliferation • response to drug • purine-containing compound salvage • small molecule metabolic process • positive regulation of alpha-beta T cell differentiation • nucleobase-containing small molecule metabolic process • interleukin-2 secretion Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	4860	18950
Ensembl	ENSG00000198805	ENSMUSG00000021871
UniProt	P00491	P23492
RefSeq (mRNA)	NM_000270	NM_013632
RefSeq (protein)	NP_000261	NP_038660
Location (UCSC)	Chr 14: 20.94 – 20.95 Mb	Chr 14: 50.94 – 50.97 Mb
PubMed search	[1]	[2]

Purine nucleoside phosphorylase also known as PNPase and inosine phosphorylase is an enzyme that in humans is encoded by the NP gene.

Function

Purine nucleoside phosphorylase is an enzyme involved in purine metabolism. PNP metabolizes adenosine into adenine, inosine into hypoxanthine, and guanosine into guanine, in each case creating ribose phosphate.

Nucleoside phosphorylase is an enzyme which cleaves a nucleoside by phosphorylating the ribose to produce a nucleobase and ribose 1 phosphate. It is one enzyme of the nucleotide salvage pathways. These pathways allow the cell to produce nucleotide monophosphates when the de novo synthesis pathway has been interrupted or is non-existent (as is the case in the brain). Often the de novo pathway is interrupted as a result of chemotherapy drugs such as methotrexate or aminopterin.

All salvage pathway enzymes require a high energy phosphate donor such as ATP or PRPP.

• Thymidine can be phosphorylated by thymidine kinase (TK).
• Uridine can be phosphorylated by uridine kinase (UK).
• Cytidine can be phosphorylated by cytidine kinase (CK).
• Deoxycytidine can be phosphorylated by deoxycytidine kinase (DCK).

Adenosine uses the enzyme adenosine kinase, which is a very important enzyme in the cell. Attempts are being made to develop an inhibitor for the enzyme for use in cancer chemotherapy.

Enzyme regulation

This protein may use the morpheein model of allosteric regulation.

Clinical significance

PNPase together with adenosine deaminase (ADA), serves a key role in purine catabolism, referred to as the salvage pathway. Mutations in ADA lead to an accumulation of (d)ATP, which inhibits ribonucleotide reductase, leading to a deficiency in (d)CTPs and (d)TTPs, which, in turn, induces apoptosis in T-lymphocytes and B-lymphocytes, leading to severe combined immunodeficiency (SCID).^{citation needed}

PNP-deficient patients will have an immunodeficiency problem. It affects only T-cells; B-cells are unaffected by the deficiency.

See also

• Purine nucleoside phosphorylase deficiency

Further reading

• Markert ML (1991). "Purine nucleoside phosphorylase deficiency.". Immunodeficiency reviews 3 (1): 45–81. PMID 1931007. 
• Borgers M, Verhaegen H, De Brabander M, et al. (1978). "Purine nucleoside phosphorylase in chronic lymphocytic leukemia (CLL).". Blood 52 (5): 886–95. PMID 100152. 
• Aust MR, Andrews LG, Barrett MJ, et al. (1992). "Molecular analysis of mutations in a patient with purine nucleoside phosphorylase deficiency.". Am. J. Hum. Genet. 51 (4): 763–72. PMC 1682776. PMID 1384322. 
• Andrews LG, Markert ML (1992). "Exon skipping in purine nucleoside phosphorylase mRNA processing leading to severe immunodeficiency.". J. Biol. Chem. 267 (11): 7834–8. PMID 1560016. 
• Jonsson JJ, Williams SR, McIvor RS (1991). "Sequence and functional characterization of the human purine nucleoside phosphorylase promoter.". Nucleic Acids Res. 19 (18): 5015–20. doi:10.1093/nar/19.18.5015. PMC 328804. PMID 1923769. 
• Ealick SE, Rule SA, Carter DC, et al. (1990). "Three-dimensional structure of human erythrocytic purine nucleoside phosphorylase at 3.2 A resolution.". J. Biol. Chem. 265 (3): 1812–20. PMID 2104852. 
• Williams SR, Gekeler V, McIvor RS, Martin DW (1987). "A human purine nucleoside phosphorylase deficiency caused by a single base change.". J. Biol. Chem. 262 (5): 2332–8. PMID 3029074. 
• Williams SR, Goddard JM, Martin DW (1984). "Human purine nucleoside phosphorylase cDNA sequence and genomic clone characterization.". Nucleic Acids Res. 12 (14): 5779–87. doi:10.1093/nar/12.14.5779. PMC 320030. PMID 6087295. 
• Pannicke U, Tuchschmid P, Friedrich W, et al. (1997). "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.". Hum. Genet. 98 (6): 706–9. doi:10.1007/s004390050290. PMID 8931706. 
• Markert ML, Finkel BD, McLaughlin TM, et al. (1997). "Mutations in purine nucleoside phosphorylase deficiency.". Hum. Mutat. 9 (2): 118–21. doi:10.1002/(SICI)1098-1004(1997)9:2<118::AID-HUMU3>3.0.CO;2-5. PMID 9067751. 
• Erion MD, Takabayashi K, Smith HB, et al. (1997). "Purine nucleoside phosphorylase. 1. Structure-function studies.". Biochemistry 36 (39): 11725–34. doi:10.1021/bi961969w. PMID 9305962. 
• Erion MD, Stoeckler JD, Guida WC, et al. (1997). "Purine nucleoside phosphorylase. 2. Catalytic mechanism.". Biochemistry 36 (39): 11735–48. doi:10.1021/bi961970v. PMID 9305963. 
• Stoeckler JD, Poirot AF, Smith RM, et al. (1997). "Purine nucleoside phosphorylase. 3. Reversal of purine base specificity by site-directed mutagenesis.". Biochemistry 36 (39): 11749–56. doi:10.1021/bi961971n. PMID 9305964. 
• Sasaki Y, Iseki M, Yamaguchi S, et al. (1998). "Direct evidence of autosomal recessive inheritance of Arg24 to termination codon in purine nucleoside phosphorylase gene in a family with a severe combined immunodeficiency patient.". Hum. Genet. 103 (1): 81–5. doi:10.1007/s004390050787. PMID 9737781. 
• Sheppard TL, Ordoukhanian P, Joyce GF (2000). "A DNA enzyme with N-glycosylase activity.". Proc. Natl. Acad. Sci. U.S.A. 97 (14): 7802–7. doi:10.1073/pnas.97.14.7802. PMC 16625. PMID 10884411. 
• Dalal I, Grunebaum E, Cohen A, Roifman CM (2001). "Two novel mutations in a purine nucleoside phosphorylase (PNP)-deficient patient.". Clin. Genet. 59 (6): 430–7. doi:10.1034/j.1399-0004.2001.590608.x. PMID 11453975. 
• Ivings L, Pennington SR, Jenkins R, et al. (2002). "Identification of Ca2+-dependent binding partners for the neuronal calcium sensor protein neurocalcin delta: interaction with actin, clathrin and tubulin.". Biochem. J. 363 (Pt 3): 599–608. doi:10.1042/0264-6021:3630599. PMC 1222513. PMID 11964161. 
• Falkenberg M, Gaspari M, Rantanen A, et al. (2002). "Mitochondrial transcription factors B1 and B2 activate transcription of human mtDNA.". Nat. Genet. 31 (3): 289–94. doi:10.1038/ng909. PMID 12068295. 
• Stoychev G, Kierdaszuk B, Shugar D (2002). "Xanthosine and xanthine. Substrate properties with purine nucleoside phosphorylases, and relevance to other enzyme systems.". Eur. J. Biochem. 269 (16): 4048–57. doi:10.1046/j.1432-1033.2002.03097.x. PMID 12180982. 

External links

• Human PNP at Cornell University
• E. Coli PNP at Cornell University
• Purine-Nucleoside Phosphorylase at the US National Library of Medicine Medical Subject Headings (MeSH)