1rr6

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{{Seed}}
 
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[[Image:1rr6.png|left|200px]]
 
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==Structure of human purine nucleoside phosphorylase in complex with Immucillin-H and phosphate==
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The line below this paragraph, containing "STRUCTURE_1rr6", creates the "Structure Box" on the page.
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<StructureSection load='1rr6' size='340' side='right'caption='[[1rr6]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[1rr6]] 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=1RR6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1RR6 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IMH:1,4-DIDEOXY-4-AZA-1-(S)-(9-DEAZAHYPOXANTHIN-9-YL)-D-RIBITOL'>IMH</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
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{{STRUCTURE_1rr6| PDB=1rr6 | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1rr6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rr6 OCA], [https://pdbe.org/1rr6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1rr6 RCSB], [https://www.ebi.ac.uk/pdbsum/1rr6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1rr6 ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[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>
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== Function ==
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[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>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/rr/1rr6_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1rr6 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Purine nucleoside phosphorylase from Plasmodium falciparum (PfPNP) is an anti-malarial target based on the activity of Immucillins. The crystal structure of PfPNP.Immucillin-H (ImmH).SO(4) reveals a homohexamer with ImmH and SO(4) bound at each catalytic site. A solvent-filled cavity close to the 5'-hydroxyl group of ImmH suggested that PfPNP can accept additional functional groups at the 5'-carbon. Assays established 5'-methylthioinosine (MTI) as a substrate for PfPNP. MTI is not found in human metabolism. These properties of PfPNP suggest unusual purine pathways in P. falciparum and provide structural and mechanistic foundations for the design of malaria-specific transition state analogue inhibitors. 5'-Methylthio-Immucillin-H (MT-ImmH) was designed to resemble the transition state of PfPNP and binds to PfPNP and human-PNP with K(d) values of 2.7 and 303 nm, respectively, to give a discrimination factor of 112. MT-ImmH is the first inhibitor that favors PfPNP inhibition. The structure of PfPNP.MT-ImmH.SO(4) shows that the hydrophobic methylthio group inserts into a hydrophobic region adjacent to the more hydrophilic 5'-hydroxyl binding site of ImmH. The catalytic features of PfPNP indicate a dual cellular function in purine salvage and polyamine metabolism. Combined metabolic functions in a single enzyme strengthen the rationale for targeting PfPNP in anti-malarial action.
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===Structure of human purine nucleoside phosphorylase in complex with Immucillin-H and phosphate===
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Plasmodium falciparum purine nucleoside phosphorylase: crystal structures, immucillin inhibitors, and dual catalytic function.,Shi W, Ting LM, Kicska GA, Lewandowicz A, Tyler PC, Evans GB, Furneaux RH, Kim K, Almo SC, Schramm VL J Biol Chem. 2004 Apr 30;279(18):18103-6. Epub 2004 Feb 23. PMID:14982926<ref>PMID:14982926</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 1rr6" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_14982926}}, adds the Publication Abstract to the page
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*[[Purine nucleoside phosphorylase 3D structures|Purine nucleoside phosphorylase 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 14982926 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_14982926}}
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__TOC__
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</StructureSection>
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==About this Structure==
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1RR6 is a 1 chain structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RR6 OCA].
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==Reference==
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<ref group="xtra">PMID:14982926</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Purine-nucleoside phosphorylase]]
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[[Category: Large Structures]]
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[[Category: Almo, S C.]]
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[[Category: Almo SC]]
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[[Category: Furneaux, R H.]]
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[[Category: Furneaux RH]]
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[[Category: Lewandowicz, A.]]
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[[Category: Lewandowicz A]]
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[[Category: Schramm, V L.]]
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[[Category: Schramm VL]]
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[[Category: Shi, W.]]
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[[Category: Shi W]]
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[[Category: Tyler, P C.]]
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[[Category: Tyler PC]]
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[[Category: Pnp]]
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[[Category: Transition state analogue]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Feb 16 20:49:09 2009''
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Current revision

Structure of human purine nucleoside phosphorylase in complex with Immucillin-H and phosphate

PDB ID 1rr6

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