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| | <StructureSection load='1m73' size='340' side='right'caption='[[1m73]], [[Resolution|resolution]] 2.30Å' scene=''> | | <StructureSection load='1m73' size='340' side='right'caption='[[1m73]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1m73]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M73 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1M73 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1m73]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M73 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1M73 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1ula|1ula]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Purine-nucleoside_phosphorylase Purine-nucleoside phosphorylase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.1 2.4.2.1] </span></td></tr>
| + | |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1m73 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m73 OCA], [https://pdbe.org/1m73 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1m73 RCSB], [https://www.ebi.ac.uk/pdbsum/1m73 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1m73 ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1m73 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m73 OCA], [https://pdbe.org/1m73 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1m73 RCSB], [https://www.ebi.ac.uk/pdbsum/1m73 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1m73 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[https://www.uniprot.org/uniprot/PNPH_HUMAN PNPH_HUMAN]] Defects in PNP are the cause of purine nucleoside phosphorylase deficiency (PNPD) [MIM:[https://omim.org/entry/613179 613179]]. It leads to a severe T-cell immunodeficiency with neurologic disorder in children.<ref>PMID:3029074</ref> <ref>PMID:1384322</ref> <ref>PMID:8931706</ref>
| + | [https://www.uniprot.org/uniprot/PNPH_HUMAN PNPH_HUMAN] Defects in PNP are the cause of purine nucleoside phosphorylase deficiency (PNPD) [MIM:[https://omim.org/entry/613179 613179]. It leads to a severe T-cell immunodeficiency with neurologic disorder in children.<ref>PMID:3029074</ref> <ref>PMID:1384322</ref> <ref>PMID:8931706</ref> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/PNPH_HUMAN PNPH_HUMAN]] The purine nucleoside phosphorylases catalyze the phosphorolytic breakdown of the N-glycosidic bond in the beta-(deoxy)ribonucleoside molecules, with the formation of the corresponding free purine bases and pentose-1-phosphate.<ref>PMID:2104852</ref>
| + | [https://www.uniprot.org/uniprot/PNPH_HUMAN PNPH_HUMAN] The purine nucleoside phosphorylases catalyze the phosphorolytic breakdown of the N-glycosidic bond in the beta-(deoxy)ribonucleoside molecules, with the formation of the corresponding free purine bases and pentose-1-phosphate.<ref>PMID:2104852</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Purine-nucleoside phosphorylase]]
| + | [[Category: Basso LA]] |
| - | [[Category: Azevedo, W F.De]]
| + | [[Category: Canduri F]] |
| - | [[Category: Basso, L A]] | + | [[Category: De Azevedo Jr WF]] |
| - | [[Category: Canduri, F]] | + | [[Category: Marangoni Dos Santos D]] |
| - | [[Category: Olivieri, J R]] | + | [[Category: Olivieri JR]] |
| - | [[Category: Palma, M S]] | + | [[Category: Palma MS]] |
| - | [[Category: Santos, D Marangoni Dos]]
| + | [[Category: Santos DS]] |
| - | [[Category: Santos, D S]]
| + | [[Category: Santos GC]] |
| - | [[Category: Santos, G C]] | + | [[Category: Silva RG]] |
| - | [[Category: Silva, R G]] | + | |
| - | [[Category: Drug design]] | + | |
| - | [[Category: Purine nucleoside phosphorylase]] | + | |
| - | [[Category: Synchrotron]] | + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Disease
PNPH_HUMAN Defects in PNP are the cause of purine nucleoside phosphorylase deficiency (PNPD) [MIM:613179. It leads to a severe T-cell immunodeficiency with neurologic disorder in children.[1] [2] [3]
Function
PNPH_HUMAN The purine nucleoside phosphorylases catalyze the phosphorolytic breakdown of the N-glycosidic bond in the beta-(deoxy)ribonucleoside molecules, with the formation of the corresponding free purine bases and pentose-1-phosphate.[4]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Purine nucleoside phosphorylase (PNP) catalyzes the phosphorolysis of the N-ribosidic bonds of purine nucleosides and deoxynucleosides. In human, PNP is the only route for degradation of deoxyguanosine and genetic deficiency of this enzyme leads to profound T-cell mediated immunosuppression. PNP is therefore a target for inhibitor development aiming at T-cell immune response modulation and its low resolution structure has been used for drug design. Here we report the structure of human PNP solved to 2.3A resolution using synchrotron radiation and cryocrystallographic techniques. This structure allowed a more precise analysis of the active site, generating a more reliable model for substrate binding. The higher resolution data allowed the identification of water molecules in the active site, which suggests binding partners for potential ligands. Furthermore, the present structure may be used in the new structure-based design of PNP inhibitors.
Crystal structure of human purine nucleoside phosphorylase at 2.3A resolution.,de Azevedo WF Jr, Canduri F, dos Santos DM, Silva RG, de Oliveira JS, de Carvalho LP, Basso LA, Mendes MA, Palma MS, Santos DS Biochem Biophys Res Commun. 2003 Aug 29;308(3):545-52. PMID:12914785[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Williams SR, Gekeler V, McIvor RS, Martin DW Jr. A human purine nucleoside phosphorylase deficiency caused by a single base change. J Biol Chem. 1987 Feb 15;262(5):2332-8. PMID:3029074
- ↑ Aust MR, Andrews LG, Barrett MJ, Norby-Slycord CJ, Markert ML. Molecular analysis of mutations in a patient with purine nucleoside phosphorylase deficiency. Am J Hum Genet. 1992 Oct;51(4):763-72. PMID:1384322
- ↑ Pannicke U, Tuchschmid P, Friedrich W, Bartram CR, Schwarz K. 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. 1996 Dec;98(6):706-9. PMID:8931706
- ↑ Ealick SE, Rule SA, Carter DC, Greenhough TJ, Babu YS, Cook WJ, Habash J, Helliwell JR, Stoeckler JD, Parks RE Jr, et al.. Three-dimensional structure of human erythrocytic purine nucleoside phosphorylase at 3.2 A resolution. J Biol Chem. 1990 Jan 25;265(3):1812-20. PMID:2104852
- ↑ de Azevedo WF Jr, Canduri F, dos Santos DM, Silva RG, de Oliveira JS, de Carvalho LP, Basso LA, Mendes MA, Palma MS, Santos DS. Crystal structure of human purine nucleoside phosphorylase at 2.3A resolution. Biochem Biophys Res Commun. 2003 Aug 29;308(3):545-52. PMID:12914785
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