Purine nucleoside phosphorylase: Difference between revisions

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{{Mergeto|Nucleoside phosphorylase|date=April 2008}}<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->
{{Inline citations|date=September 2017}}{{Distinguish|polynucleotide phosphorylase}}
{{PBB_Controls
{{enzyme
| update_page = yes
| Name = purine-nucleoside phosphorylase
| require_manual_inspection = no
| EC_number = 2.4.2.1
| update_protein_box = yes
| CAS_number = 9030-21-1
| update_summary = yes
| IUBMB_EC_number = 2/4/2/1
| update_citations = yes
| GO_code = 0004731
| image = 1rct.png
| width =  
| caption = purine-nucleoside phosphorylase. [[Protein Data Bank|PDB]] 1rct.<ref>{{cite journal | vauthors = Canduri F, dos Santos DM, Silva RG, Mendes MA, Basso LA, Palma MS, de Azevedo WF, Santos DS | title = Structures of human purine nucleoside phosphorylase complexed with inosine and ddI | journal = Biochemical and Biophysical Research Communications | volume = 313 | issue = 4 | pages = 907–14 | date = Jan 2004 | pmid = 14706628 | doi = 10.1016/j.bbrc.2003.11.179 }}</ref>
}}
}}
{{Infobox_gene}}
'''Purine nucleoside phosphorylase''' ('''PNP''') also known as '''PNPase''' and '''inosine phosphorylase''' is an [[enzyme]] that in humans is encoded by the ''NP'' [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: NP nucleoside phosphorylase| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4860| accessdate = }}</ref>


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
In [[enzymology]], a purine-nucleoside phosphorylase ({{EC number|2.4.2.1}}) is an [[enzyme]] that [[catalysis|catalyzes]] the [[chemical reaction]]
{{GNF_Protein_box
 
| image = PBB_Protein_NP_image.jpg
:purine nucleoside + phosphate <math>\rightleftharpoons</math> purine + alpha-D-ribose 1-phosphate
| image_source = [[Protein Data Bank|PDB]] rendering based on 1m73.
 
| PDB = {{PDB2|1m73}}, {{PDB2|1pf7}}, {{PDB2|1pwy}}, {{PDB2|1rct}}, {{PDB2|1rfg}}, {{PDB2|1rr6}}, {{PDB2|1rsz}}, {{PDB2|1rt9}}, {{PDB2|1ula}}, {{PDB2|1ulb}}, {{PDB2|1v2h}}, {{PDB2|1v3q}}, {{PDB2|1v41}}, {{PDB2|1v45}}, {{PDB2|1yry}}, {{PDB2|2a0w}}, {{PDB2|2a0x}}, {{PDB2|2a0y}}, {{PDB2|2oc4}}, {{PDB2|2oc9}}, {{PDB2|2on6}}
Thus, the two [[substrate (biochemistry)|substrates]] of this enzyme are [[purine nucleoside]] and [[phosphate]], whereas its two [[product (chemistry)|products]] are [[purine]] and [[alpha-D-ribose 1-phosphate]].
| Name = Nucleoside phosphorylase
 
| HGNCid = 7892
== Nomenclature ==
| Symbol = NP
 
| AltSymbols =; MGC117396; MGC125915; MGC125916; PNP; PRO1837; PUNP
This enzyme belongs to the family of [[glycosyltransferase]]s, specifically the pentosyltransferases.  The [[List of enzymes|systematic name]] of this enzyme class is '''purine-nucleoside:phosphate ribosyltransferase'''.
| OMIM = 164050
 
| ECnumber = 2.4.2.1
Other names in common use include:
| Homologene = 227
{{div col|colwidth=20em}}
| MGIid = 
* inosine phosphorylase,
| GeneAtlas_image1 = PBB_GE_NP_201695_s_at_tn.png
* PNPase,
  | Function = {{GNF_GO|id=GO:0004731 |text = purine-nucleoside phosphorylase activity}}
* PUNPI,
| Component =
* PUNPII,
| Process = {{GNF_GO|id=GO:0006139 |text = nucleobase, nucleoside, nucleotide and nucleic acid metabolic process}} {{GNF_GO|id=GO:0006304 |text = DNA modification}}  
* inosine-guanosine phosphorylase,
| Orthologs = {{GNF_Ortholog_box
* nucleotide phosphatase,
    | Hs_EntrezGene = 4860
* purine deoxynucleoside phosphorylase,
    | Hs_Ensembl = ENSG00000198805
* purine deoxyribonucleoside phosphorylase,
    | Hs_RefseqProtein = NP_000261
* purine nucleoside phosphorylase,
    | Hs_RefseqmRNA = NM_000270
* and purine ribonucleoside phosphorylase.  
    | Hs_GenLoc_db = 
{{Div col end}}
    | Hs_GenLoc_chr = 14
 
    | Hs_GenLoc_start = 20007409
This enzyme participates in 3 [[metabolism|metabolic pathways]]: [[purine metabolism]], [[pyrimidine metabolism]], and [[nicotinate and nicotinamide metabolism]].
    | Hs_GenLoc_end = 20015082
 
    | Hs_Uniprot = P00491
== Function ==
    | Mm_EntrezGene =  
Purine nucleoside phosphorylase is an enzyme involved in [[Purine#Metabolism|purine metabolism]]. PNP metabolizes [[inosine]] into [[hypoxanthine]] and [[guanosine]] into [[guanine]], in each case creating [[ribose phosphate]]. Note: [[adenosine]] is first metabolized to  [[inosine]] via the enzyme adenosine deaminase.<ref>Kaplan USMLE Biochemistry Review</ref>
    | Mm_Ensembl = 
 
    | Mm_RefseqmRNA = 
Nucleoside phosphorylase is an enzyme which cleaves a nucleoside by [[Phosphorylation|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|''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]].
    | Mm_RefseqProtein = 
 
    | Mm_GenLoc_db = 
All salvage pathway enzymes require a high energy [[phosphate]] donor such as [[Adenosine triphosphate|ATP]] or [[PRPP]].
    | Mm_GenLoc_chr =
 
    | Mm_GenLoc_start =
* [[Thymidine]] can be phosphorylated by [[thymidine kinase]] (TK).
    | Mm_GenLoc_end =
* [[Uridine]] can be phosphorylated by [[uridine kinase]] (UK).
    | Mm_Uniprot =
* [[Cytidine]] can be phosphorylated by [[cytidine kinase]] (CK).
  }}
* [[Deoxycytidine]] can be phosphorylated by [[deoxycytidine kinase]] (DCK).
}}
 
'''Purine nucleoside phosphorylase''' (also known as '''PNPase''') is an [[enzyme]] ({{EC number|2.4.2.1}}) involved in [[Purine#Metabolism|purine metabolism]]. PNP metabolizes [[adenosine]] into [[adenine]], [[inosine]] into [[hypoxanthine]], and [[guanosine]] into [[guanine]], in each case creating [[ribose phosphate]].
[[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.
<!-- The PBB_Summary template is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
 
{{PBB_Summary
== Enzyme regulation ==
| section_title =
 
| summary_text = NP encodes the enzyme purine nucleoside phosphorylase that together with adenosine deaminase (ADA) serves a key role in purine catabolism, referred to as the salvage pathway. Mutations in either enzyme result in a severe combined immunodeficiency (SCID).<ref name="entrez">{{cite web | title = Entrez Gene: NP nucleoside phosphorylase| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4860| accessdate = }}</ref>
This protein may use the [[morpheein]] model of [[allosteric regulation]].<ref name=pmid22182754>{{cite journal | vauthors = Selwood T, Jaffe EK | title = Dynamic dissociating homo-oligomers and the control of protein function | journal = Archives of Biochemistry and Biophysics | volume = 519 | issue = 2 | pages = 131–43 | date = Mar 2012 | pmid = 22182754 | pmc = 3298769 | doi = 10.1016/j.abb.2011.11.020 }}</ref>
}}
 
Confusingly, the same abbreviation (''PNPase''), is also used for another, otherwise unrelated, enzyme, namely [[Polynucleotide Phosphorylase]].
== 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|date=November 2010}}


Diseases linked to PNP:
PNP-deficient patients will have an immunodeficiency problem.  It affects only T-cells; B-cells are unaffected by the deficiency.
PNP deficient patients will have an immunodeficiency problem.  Curiously, it affects only T-cells, B-cells are unaffected by the deficiency.


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


==External links==
== References ==
{{reflist}}
 
== Further reading ==
{{Refbegin| 2}}
* {{cite journal | vauthors = Markert ML | title = Purine nucleoside phosphorylase deficiency | journal = Immunodeficiency Reviews | volume = 3 | issue = 1 | pages = 45–81 | year = 1991 | pmid = 1931007 | doi =  }}
* {{cite journal | vauthors = Borgers M, Verhaegen H, De Brabander M, De Cree J, De Cock W, Thoné F, Geuens G | title = Purine nucleoside phosphorylase in chronic lymphocytic leukemia (CLL) | journal = Blood | volume = 52 | issue = 5 | pages = 886–95 | date = Nov 1978 | pmid = 100152 | doi =  }}
* {{cite journal | vauthors = Aust MR, Andrews LG, Barrett MJ, Norby-Slycord CJ, Markert ML | title = Molecular analysis of mutations in a patient with purine nucleoside phosphorylase deficiency | journal = American Journal of Human Genetics | volume = 51 | issue = 4 | pages = 763–72 | date = Oct 1992 | pmid = 1384322 | pmc = 1682776 | doi =  }}
* {{cite journal | vauthors = Andrews LG, Markert ML | title = Exon skipping in purine nucleoside phosphorylase mRNA processing leading to severe immunodeficiency | journal = The Journal of Biological Chemistry | volume = 267 | issue = 11 | pages = 7834–8 | date = Apr 1992 | pmid = 1560016 | doi =  }}
* {{cite journal | vauthors = Jonsson JJ, Williams SR, McIvor RS | title = Sequence and functional characterization of the human purine nucleoside phosphorylase promoter | journal = Nucleic Acids Research | volume = 19 | issue = 18 | pages = 5015–20 | date = Sep 1991 | pmid = 1923769 | pmc = 328804 | doi = 10.1093/nar/19.18.5015 }}
* {{cite journal | vauthors = Ealick SE, Rule SA, Carter DC, Greenhough TJ, Babu YS, Cook WJ, Habash J, Helliwell JR, Stoeckler JD, Parks RE | title = Three-dimensional structure of human erythrocytic purine nucleoside phosphorylase at 3.2 A resolution | journal = The Journal of Biological Chemistry | volume = 265 | issue = 3 | pages = 1812–20 | date = Jan 1990 | pmid = 2104852 | doi =  }}
* {{cite journal | vauthors = Williams SR, Gekeler V, McIvor RS, Martin DW | title = A human purine nucleoside phosphorylase deficiency caused by a single base change | journal = The Journal of Biological Chemistry | volume = 262 | issue = 5 | pages = 2332–8 | date = Feb 1987 | pmid = 3029074 | doi =  }}
* {{cite journal | vauthors = Williams SR, Goddard JM, Martin DW | title = Human purine nucleoside phosphorylase cDNA sequence and genomic clone characterization | journal = Nucleic Acids Research | volume = 12 | issue = 14 | pages = 5779–87 | date = Jul 1984 | pmid = 6087295 | pmc = 320030 | doi = 10.1093/nar/12.14.5779 }}
* {{cite journal | vauthors = Pannicke U, Tuchschmid P, Friedrich W, Bartram CR, Schwarz K | title = 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 | journal = Human Genetics | volume = 98 | issue = 6 | pages = 706–9 | date = Dec 1996 | pmid = 8931706 | doi = 10.1007/s004390050290 }}
* {{cite journal | vauthors = Markert ML, Finkel BD, McLaughlin TM, Watson TJ, Collard HR, McMahon CP, Andrews LG, Barrett MJ, Ward FE | title = Mutations in purine nucleoside phosphorylase deficiency | journal = Human Mutation | volume = 9 | issue = 2 | pages = 118–21 | year = 1997 | pmid = 9067751 | doi = 10.1002/(SICI)1098-1004(1997)9:2<118::AID-HUMU3>3.0.CO;2-5 }}
* {{cite journal | vauthors = Erion MD, Takabayashi K, Smith HB, Kessi J, Wagner S, Hönger S, Shames SL, Ealick SE | title = Purine nucleoside phosphorylase. 1. Structure-function studies | journal = Biochemistry | volume = 36 | issue = 39 | pages = 11725–34 | date = Sep 1997 | pmid = 9305962 | doi = 10.1021/bi961969w }}
* {{cite journal | vauthors = Erion MD, Stoeckler JD, Guida WC, Walter RL, Ealick SE | title = Purine nucleoside phosphorylase. 2. Catalytic mechanism | journal = Biochemistry | volume = 36 | issue = 39 | pages = 11735–48 | date = Sep 1997 | pmid = 9305963 | doi = 10.1021/bi961970v }}
* {{cite journal | vauthors = Stoeckler JD, Poirot AF, Smith RM, Parks RE, Ealick SE, Takabayashi K, Erion MD | title = Purine nucleoside phosphorylase. 3. Reversal of purine base specificity by site-directed mutagenesis | journal = Biochemistry | volume = 36 | issue = 39 | pages = 11749–56 | date = Sep 1997 | pmid = 9305964 | doi = 10.1021/bi961971n }}
* {{cite journal | vauthors = Sasaki Y, Iseki M, Yamaguchi S, Kurosawa Y, Yamamoto T, Moriwaki Y, Kenri T, Sasaki T, Yamashita R | title = 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 | journal = Human Genetics | volume = 103 | issue = 1 | pages = 81–5 | date = Jul 1998 | pmid = 9737781 | doi = 10.1007/s004390050787 }}
* {{cite journal | vauthors = Sheppard TL, Ordoukhanian P, Joyce GF | title = A DNA enzyme with N-glycosylase activity | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 97 | issue = 14 | pages = 7802–7 | date = Jul 2000 | pmid = 10884411 | pmc = 16625 | doi = 10.1073/pnas.97.14.7802 }}
* {{cite journal | vauthors = Dalal I, Grunebaum E, Cohen A, Roifman CM | title = Two novel mutations in a purine nucleoside phosphorylase (PNP)-deficient patient | journal = Clinical Genetics | volume = 59 | issue = 6 | pages = 430–7 | date = Jun 2001 | pmid = 11453975 | doi = 10.1034/j.1399-0004.2001.590608.x }}
* {{cite journal | vauthors = Ivings L, Pennington SR, Jenkins R, Weiss JL, Burgoyne RD | title = Identification of Ca2+-dependent binding partners for the neuronal calcium sensor protein neurocalcin delta: interaction with actin, clathrin and tubulin | journal = The Biochemical Journal | volume = 363 | issue = Pt 3 | pages = 599–608 | date = May 2002 | pmid = 11964161 | pmc = 1222513 | doi = 10.1042/0264-6021:3630599 }}
* {{cite journal | vauthors = Falkenberg M, Gaspari M, Rantanen A, Trifunovic A, Larsson NG, Gustafsson CM | title = Mitochondrial transcription factors B1 and B2 activate transcription of human mtDNA | journal = Nature Genetics | volume = 31 | issue = 3 | pages = 289–94 | date = Jul 2002 | pmid = 12068295 | doi = 10.1038/ng909 }}
* {{cite journal | vauthors = Stoychev G, Kierdaszuk B, Shugar D | title = Xanthosine and xanthine. Substrate properties with purine nucleoside phosphorylases, and relevance to other enzyme systems | journal = European Journal of Biochemistry / FEBS | volume = 269 | issue = 16 | pages = 4048–57 | date = Aug 2002 | pmid = 12180982 | doi = 10.1046/j.1432-1033.2002.03097.x }}
* {{cite journal |vauthors=Agarwal RP, Parks RE | date = 1969 | title = Purine nucleoside phosphorylase from human erythrocytes. IV Crystallization and some properties | journal = J. Biol. Chem.  | volume = 244 | pages = 644&ndash;7  | pmid = 5768862 | issue = 4 }}
* Boyer, P.D., Lardy, H. and Myrback, K. (Eds.), The Enzymes, 2nd ed., vol. 5, Academic Press, New York, 1961, p.&nbsp;237-255.
* {{cite journal |vauthors=HEPPEL LA, HILMOE RJ | date = 1952 | title = [Phosphorolysis and hydrolysis of purine ribosides by enzymes from yeast.] | journal = J. Biol. Chem.  | volume = 198 | pages = 683&ndash;94  | pmid = 12999785 | issue = 2 }}
* {{cite journal | author = Kalckar HM | date = 1947 | title = The enzymatic synthesis of purine ribosides | journal = J. Biol. Chem.  | volume = 167 | pages = 477&ndash;486 | pmid=20285042}}
* {{cite journal |vauthors=Saunders PP, Wilson BA, Saunders GF | date = 1969 | title = Purification and comparative properties of a pyrimidine nucleoside phosphorylase from Bacillus stearothermophilus | journal = J. Biol. Chem.  | volume = 244 | pages = 3691&ndash;7  | pmid = 4978445 | issue = 13 }}
* {{cite journal |vauthors=Tsuboi KK, Hudson PB| date = 1957 | title = Enzymes of the human erythrocyte. I. Purine nucleoside phosphorylase; isolation procedure | journal = J. Biol. Chem.  | volume = 224 | pages = 879&ndash;887 | pmid=13405917}}
 
{{Refend}}
 
== External links ==
*[http://arginine.chem.cornell.edu/Structures/HumanPNP.html Human PNP] at [[Cornell University]]
*[http://arginine.chem.cornell.edu/Structures/HumanPNP.html Human PNP] at [[Cornell University]]
*[http://arginine.chem.cornell.edu/Structures/ECPNP.html E. Coli PNP] at [[Cornell University]]
*[http://arginine.chem.cornell.edu/Structures/ECPNP.html E. Coli PNP] at [[Cornell University]]
*{{MeshName|Purine-Nucleoside+Phosphorylase}}
*{{MeshName|Purine-Nucleoside+Phosphorylase}}


{{PDB Gallery|geneid=4860}}
{{Nucleotide metabolism}}
{{Glycosyltransferases}}
{{Glycosyltransferases}}
{{Nucleotide metabolism}}
{{Enzymes}}
 
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[[ar:بورين نيكليوزيد فوسفوريلاز]]
[[Category:EC 2.4.2]]
[[de:Purin-Nukleosid-Phosphorylase]]
[[Category:Enzymes of known structure]]
[[it:Purina nucleoside fosforilasi]]
[[zh:嘌呤核苷磷酸化酶]]

Latest revision as of 10:44, 17 September 2017

Not to be confused with polynucleotide phosphorylase.
purine-nucleoside phosphorylase
File:1rct.png
purine-nucleoside phosphorylase. PDB 1rct.[1]
Identifiers
EC number2.4.2.1
CAS number9030-21-1
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
VALUE_ERROR (nil)
Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

n/a

n/a

Ensembl

n/a

n/a

UniProt

n/a

n/a

RefSeq (mRNA)

n/a

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RefSeq (protein)

n/a

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

Purine nucleoside phosphorylase (PNP) also known as PNPase and inosine phosphorylase is an enzyme that in humans is encoded by the NP gene.[2]

In enzymology, a purine-nucleoside phosphorylase (EC 2.4.2.1) is an enzyme that catalyzes the chemical reaction

purine nucleoside + phosphate <math>\rightleftharpoons</math> purine + alpha-D-ribose 1-phosphate

Thus, the two substrates of this enzyme are purine nucleoside and phosphate, whereas its two products are purine and alpha-D-ribose 1-phosphate.

Nomenclature

This enzyme belongs to the family of glycosyltransferases, specifically the pentosyltransferases. The systematic name of this enzyme class is purine-nucleoside:phosphate ribosyltransferase.

Other names in common use include:

  • inosine phosphorylase,
  • PNPase,
  • PUNPI,
  • PUNPII,
  • inosine-guanosine phosphorylase,
  • nucleotide phosphatase,
  • purine deoxynucleoside phosphorylase,
  • purine deoxyribonucleoside phosphorylase,
  • purine nucleoside phosphorylase,
  • and purine ribonucleoside phosphorylase.

This enzyme participates in 3 metabolic pathways: purine metabolism, pyrimidine metabolism, and nicotinate and nicotinamide metabolism.

Function

Purine nucleoside phosphorylase is an enzyme involved in purine metabolism. PNP metabolizes inosine into hypoxanthine and guanosine into guanine, in each case creating ribose phosphate. Note: adenosine is first metabolized to inosine via the enzyme adenosine deaminase.[3]

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.

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.[4]

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

References

  1. ↑ Canduri F, dos Santos DM, Silva RG, Mendes MA, Basso LA, Palma MS, de Azevedo WF, Santos DS (Jan 2004). "Structures of human purine nucleoside phosphorylase complexed with inosine and ddI". Biochemical and Biophysical Research Communications. 313 (4): 907–14. doi:10.1016/j.bbrc.2003.11.179. PMID 14706628.
  2. ↑ "Entrez Gene: NP nucleoside phosphorylase".
  3. ↑ Kaplan USMLE Biochemistry Review
  4. ↑ Selwood T, Jaffe EK (Mar 2012). "Dynamic dissociating homo-oligomers and the control of protein function". Archives of Biochemistry and Biophysics. 519 (2): 131–43. doi:10.1016/j.abb.2011.11.020. PMC 3298769. PMID 22182754.

Further reading

  • Markert ML (1991). "Purine nucleoside phosphorylase deficiency". Immunodeficiency Reviews. 3 (1): 45–81. PMID 1931007.
  • Borgers M, Verhaegen H, De Brabander M, De Cree J, De Cock W, Thoné F, Geuens G (Nov 1978). "Purine nucleoside phosphorylase in chronic lymphocytic leukemia (CLL)". Blood. 52 (5): 886–95. PMID 100152.
  • Aust MR, Andrews LG, Barrett MJ, Norby-Slycord CJ, Markert ML (Oct 1992). "Molecular analysis of mutations in a patient with purine nucleoside phosphorylase deficiency". American Journal of Human Genetics. 51 (4): 763–72. PMC 1682776. PMID 1384322.
  • Andrews LG, Markert ML (Apr 1992). "Exon skipping in purine nucleoside phosphorylase mRNA processing leading to severe immunodeficiency". The Journal of Biological Chemistry. 267 (11): 7834–8. PMID 1560016.
  • Jonsson JJ, Williams SR, McIvor RS (Sep 1991). "Sequence and functional characterization of the human purine nucleoside phosphorylase promoter". Nucleic Acids Research. 19 (18): 5015–20. doi:10.1093/nar/19.18.5015. PMC 328804. PMID 1923769.
  • Ealick SE, Rule SA, Carter DC, Greenhough TJ, Babu YS, Cook WJ, Habash J, Helliwell JR, Stoeckler JD, Parks RE (Jan 1990). "Three-dimensional structure of human erythrocytic purine nucleoside phosphorylase at 3.2 A resolution". The Journal of Biological Chemistry. 265 (3): 1812–20. PMID 2104852.
  • Williams SR, Gekeler V, McIvor RS, Martin DW (Feb 1987). "A human purine nucleoside phosphorylase deficiency caused by a single base change". The Journal of Biological Chemistry. 262 (5): 2332–8. PMID 3029074.
  • Williams SR, Goddard JM, Martin DW (Jul 1984). "Human purine nucleoside phosphorylase cDNA sequence and genomic clone characterization". Nucleic Acids Research. 12 (14): 5779–87. doi:10.1093/nar/12.14.5779. PMC 320030. PMID 6087295.
  • Pannicke U, Tuchschmid P, Friedrich W, Bartram CR, Schwarz K (Dec 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. 98 (6): 706–9. doi:10.1007/s004390050290. PMID 8931706.
  • Markert ML, Finkel BD, McLaughlin TM, Watson TJ, Collard HR, McMahon CP, Andrews LG, Barrett MJ, Ward FE (1997). "Mutations in purine nucleoside phosphorylase deficiency". Human Mutation. 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, Kessi J, Wagner S, Hönger S, Shames SL, Ealick SE (Sep 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, Walter RL, Ealick SE (Sep 1997). "Purine nucleoside phosphorylase. 2. Catalytic mechanism". Biochemistry. 36 (39): 11735–48. doi:10.1021/bi961970v. PMID 9305963.
  • Stoeckler JD, Poirot AF, Smith RM, Parks RE, Ealick SE, Takabayashi K, Erion MD (Sep 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, Kurosawa Y, Yamamoto T, Moriwaki Y, Kenri T, Sasaki T, Yamashita R (Jul 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". Human Genetics. 103 (1): 81–5. doi:10.1007/s004390050787. PMID 9737781.
  • Sheppard TL, Ordoukhanian P, Joyce GF (Jul 2000). "A DNA enzyme with N-glycosylase activity". Proceedings of the National Academy of Sciences of the United States of America. 97 (14): 7802–7. doi:10.1073/pnas.97.14.7802. PMC 16625. PMID 10884411.
  • Dalal I, Grunebaum E, Cohen A, Roifman CM (Jun 2001). "Two novel mutations in a purine nucleoside phosphorylase (PNP)-deficient patient". Clinical Genetics. 59 (6): 430–7. doi:10.1034/j.1399-0004.2001.590608.x. PMID 11453975.
  • Ivings L, Pennington SR, Jenkins R, Weiss JL, Burgoyne RD (May 2002). "Identification of Ca2+-dependent binding partners for the neuronal calcium sensor protein neurocalcin delta: interaction with actin, clathrin and tubulin". The Biochemical Journal. 363 (Pt 3): 599–608. doi:10.1042/0264-6021:3630599. PMC 1222513. PMID 11964161.
  • Falkenberg M, Gaspari M, Rantanen A, Trifunovic A, Larsson NG, Gustafsson CM (Jul 2002). "Mitochondrial transcription factors B1 and B2 activate transcription of human mtDNA". Nature Genetics. 31 (3): 289–94. doi:10.1038/ng909. PMID 12068295.
  • Stoychev G, Kierdaszuk B, Shugar D (Aug 2002). "Xanthosine and xanthine. Substrate properties with purine nucleoside phosphorylases, and relevance to other enzyme systems". European Journal of Biochemistry / FEBS. 269 (16): 4048–57. doi:10.1046/j.1432-1033.2002.03097.x. PMID 12180982.
  • Agarwal RP, Parks RE (1969). "Purine nucleoside phosphorylase from human erythrocytes. IV Crystallization and some properties". J. Biol. Chem. 244 (4): 644&ndash, 7. PMID 5768862.
  • Boyer, P.D., Lardy, H. and Myrback, K. (Eds.), The Enzymes, 2nd ed., vol. 5, Academic Press, New York, 1961, p. 237-255.
  • HEPPEL LA, HILMOE RJ (1952). "[Phosphorolysis and hydrolysis of purine ribosides by enzymes from yeast.]". J. Biol. Chem. 198 (2): 683&ndash, 94. PMID 12999785.
  • Kalckar HM (1947). "The enzymatic synthesis of purine ribosides". J. Biol. Chem. 167: 477&ndash, 486. PMID 20285042.
  • Saunders PP, Wilson BA, Saunders GF (1969). "Purification and comparative properties of a pyrimidine nucleoside phosphorylase from Bacillus stearothermophilus". J. Biol. Chem. 244 (13): 3691&ndash, 7. PMID 4978445.
  • Tsuboi KK, Hudson PB (1957). "Enzymes of the human erythrocyte. I. Purine nucleoside phosphorylase; isolation procedure". J. Biol. Chem. 224: 879&ndash, 887. PMID 13405917.

External links

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