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Purine nucleoside phosphorylase

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<StructureSection load='1v2h' size='350' side='right' caption='Human purine nucleoside phosphorylase complex with guanine and sulfate (PDB entry [[1v2h]])' scene=''>
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<StructureSection load='' size='350' side='right' caption='Human purine nucleoside phosphorylase complex with guanine and sulfate (PDB entry [[1v2h]])' scene='57/573714/Cv/1'>
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== Function ==
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'''Purine nucleoside phosphorylase''' (PNP) cleaves nucleosides by phosphorylating ribose to produce ribose-1-phosphate. PNP metabolizes adenosine, inosine and guanosine. PNP metabolizes the waste molecules deoxyinosine and deoxyguanosine which are formed when DNA breaks down. PNP deficiency results in severe combined immunodeficiency.
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'''Purine nucleoside phosphorylase''' (PNP) cleaves nucleosides by phosphorylating ribose to produce ribose-1-phosphate. PNP metabolizes adenosine, inosine and guanosine<ref>PMID:11337031</ref>. PNP metabolizes the waste molecules deoxyinosine and deoxyguanosine which are formed when DNA breaks down.
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==3D structures of purine nucleoside phosphorylase==
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== Disease ==
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PNP deficiency results in severe combined immunodeficiency<ref>PMID:1931007</ref>.
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[[1ula]], [[1m73]] – hPNP – human<br />
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== Structural highlights ==
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[[1pbn]] – bPNP – bovine<br />
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[[1odk]], [[1odl]] – TtPNP – ''Thermus thermophilus'' <br />
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[[1z33]] – TvPNP – ''Trichomonas vaginalis''<br />
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[[1tcv]], [[1td1]] – SmPNP – ''Schistosoma masoni''<br />
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[[2b94]] – PNP – ''Plasmodium knowlesi'' <br />
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[[4mar]] – MrPNP – ''Meiothermus ruber''<br />
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===PNP binary complex with phosphate===
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<scene name='57/573714/Cv/5'>Residues 241-265 of PNP act as a gate that opens upon substrate binding</scene>. The ribose binding site is composed of mostly hydrophobic side chains<ref>PMID:14680831</ref>. <scene name='57/573714/Cv/6'>Active site</scene>.
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[[1a9o]], [[3pnp]], [[4pnp]] – bPNP + phosphate<br />
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==3D structures of purine nucleoside phosphorylase==
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[[1qe5]] – CePNP + phosphate - ''Cellulomonas''<br />
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[[Purine nucleoside phosphorylase 3D structures]]
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[[1tcu]] – SmPNP + phosphate <br />
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[[3khs]] – PNP + phosphate – grouper iridovirus<br />
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[[4gka]] – hPNP (mutant) + phosphate<br />
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[[4m3n]] – MrPNP + phosphate <br />
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[[4m7w]] – PNP + phosphate – ''Leptotrichia buccalis''<br />
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===PNP complex with guanine and derivatives===
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[[1ulb]], [[1v2h]] – hPNP + guanine<br />
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[[4ece]] – hPNP (mutant) + guanine<br />
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[[1rfg]] – hPNP + guanosine<br />
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[[1yry]], [[3iny]] – hPNP + guanine derivative <br />
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[[1v48]], [[2ai1]], [[2ai3]], [[3fuc]] – bPNP + guanine derivative <br />
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[[3e9z]] – SmPNP + guanine derivative <br />
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[[3iex]] – SmPNP + guanosine<br />
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[[1odj]] – TtPNP + guanosine<br />
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[[1vmk]] – PNP + guanine – ''Thermotoga maritima'' <br />
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[[3iom]] – MtPNP + guanine derivative - ''Mycobacterium tuberculosis'' <br />
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[[1b8n]] – bPNP + guanine derivative + phosphate<br />
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[[1c3x]] – CePNP + guanine derivative + phosphate<br />
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[[1pwy]], [[1v41]], [[1v45]] – hPNP + antiviral drug <br />
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===PNP complex with inosine and derivatives===
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[[1rct]] – hPNP + inosine <br />
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[[1a9q]], [[1a9s]] – bPNP + inosine <br />
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[[3faz]] – SmPNP + inosine <br />
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[[2ai2]] – bPNP + inosine derivative <br />
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[[1z38]] – TvPNP + inosine <br />
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[[1z39]] – TvPNP + deoxyinosine <br />
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[[1a9t]], [[1a9p]] – bPNP + deazainosine + phosphate<br />
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[[1v3q]] – hPNP + anti HIV drug <br />
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===PNP complex with xanthine and derivatives===
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[[1pf7]], [[1rr6]], [[1rsz]], [[1rt9]], [[3k8o]], [[3k8q]] – hPNP + transition state analog <br />
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[[2on6]] – hPNP (mutant) + transition state analog <br />
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[[1vfn]], [[1a9r]] – bPNP + hypoxanthine<br />
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[[3fnq]] – SmPNP + hypoxanthine<br />
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[[3scz]] – MtPNP + hypoxanthine<br />
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[[2a0w]], [[2a0x]], [[2a0y]], [[2oc4]], [[2oc9]] – hPNP (mutant) + hypoxanthine derivative <br />
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[[3odg]] – PNP + xanthine – ''Yersinia pseudotuberculosis''<br />
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[[1b8o]], [[1g2o]] – bPNP + hypoxanthine derivative + phosphate<br />
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[[3bgs]] – bPNP + transition state analog + phosphate<br />
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[[2q7o]], [[3phb]] – hPNP + transition state analog + phosphate<br />
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[[4ear]], [[4eb8]] – hPNP (mutant) + transition state analog + phosphate<br />
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[[3mb8]] – PNP + transition state analog + phosphate – ''Toxoplasma gondii''<br />
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[[1n3i]] – MtPNP + deazahypoxanthine + phosphate <br />
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[[1i80]] – MtPNP + iminoribitol + deazahypoxanthine + phosphate <br />
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===PNP complex with adenine and derivatives===
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[[1odi]] – TtPNP + adenosine <br />
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[[1z34]], [[1z35]] – TvPNP + adenosine derivative <br />
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[[4ns1]] – PgPNP + adenosine derivative – ''Porphyromonas gingivalis''<br />
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[[4nsn]] – PgPNP + adenine <br />
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[[3ggs]] – hPNP (mutant) + adenosine derivative <br />
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[[1z37]] – TvPNP + adenosine <br />
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[[3e9r]] – SmPNP + adenine <br />
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[[3f8w]] – SmPNP + adenosine <br />
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[[4m1e]] – PNP + adenine – ''Planctomyces limnophilus''<br />
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[[4lna]] – PNP + adenine + phosphate – ''Spirosoma linguale''<br />
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===PNP complex with purine and derivatives===
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[[1lv8]], [[1lvu]], [[2qpl]] – bPNP + purine derivative <br />
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[[3gb9]] – hPNP (mutant) + purine derivative <br />
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[[1fxu]] – bPNP + purine derivative + phosphate<br />
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[[1z36]] – TvPNP + antibiotic<br />
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[[3djf]] – SmPNP + inhibitor<br />
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===Other PNP complexes===
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</StructureSection>
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[[3d1v]] – hPNP + mercapto-quinazolinone<br />
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== References ==
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[[3e0q]] – SmPNP + pyrimidine derivative<br />
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<references/>
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[[3fb1]] – SmPNP + ribose-1-phosphate <br />
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[[Category:Topic Page]]

Current revision

Human purine nucleoside phosphorylase complex with guanine and sulfate (PDB entry 1v2h)

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References

  1. ↑ Bzowska A, Kulikowska E, Shugar D. Purine nucleoside phosphorylases: properties, functions, and clinical aspects. Pharmacol Ther. 2000 Dec;88(3):349-425. PMID:11337031
  2. ↑ Markert ML. Purine nucleoside phosphorylase deficiency. Immunodefic Rev. 1991;3(1):45-81. PMID:1931007
  3. ↑ de Azevedo WF Jr, Canduri F, dos Santos DM, Pereira JH, Bertacine Dias MV, Silva RG, Mendes MA, Basso LA, Palma MS, Santos DS. Crystal structure of human PNP complexed with guanine. Biochem Biophys Res Commun. 2003 Dec 19;312(3):767-72. PMID:14680831 doi:10.1016/j.bbrc.2003.10.190

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Michal Harel, Alexander Berchansky, Joel L. Sussman

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