関: N-glycosyl hydrolase

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/03/04 16:31:34」(JST)

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

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.

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.^[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.

References

^ Canduri, F.; Dos Santos, D. M.; Silva, R. G.; Mendes, M. A.; Basso, L. A.; Palma, M. S.; De Azevedo, W. F.; Santos, D. S. (2004). "Structures of human purine nucleoside phosphorylase complexed with inosine and ddI". Biochemical and Biophysical Research Communications 313 (4): 907–914. doi:10.1016/j.bbrc.2003.11.179. PMID 14706628.
^ "Entrez Gene: NP nucleoside phosphorylase".
^ Kaplan USMLE Biochemistry Review
^ 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.

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)

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Related Pictures

★リンクテーブル★

リンク元	「N-glycosyl hydrolase」「ヌクレオシダーゼ」
拡張検索	「NAD nucleosidase」「NAD+ nucleosidase」

「N-glycosyl hydrolase」

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; • nucleus; • cytoplasm; • cytosol; • cytoskeleton; • extracellular exosome;
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
	v; t; e;

Search
PMC	articles
PubMed	articles
NCBI	proteins

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