1v2h

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[[Image:1v2h.jpg|left|200px]]<br /><applet load="1v2h" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1v2h, resolution 2.70&Aring;" />
 
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'''Crystal structure of human PNP complexed with guanine'''<br />
 
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==Overview==
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==Crystal structure of human PNP complexed with guanine==
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Purine nucleoside phosphorylase (PNP) catalyzes the phosphorolysis of the, N-ribosidic bonds of purine nucleosides and deoxynucleosides. PNP is a, target for inhibitor development aiming at T-cell immune response, modulation and has been submitted to extensive structure-based drug, design. More recently, the 3-D structure of human PNP has been refined to, 2.3A resolution, which allowed a redefinition of the residues involved in, the substrate-binding sites and provided a more reliable model for, structure-based design of inhibitors. This work reports crystallographic, study of the complex of Human PNP:guanine (HsPNP:Gua) solved at 2.7A, resolution using synchrotron radiation. Analysis of the structural, differences among the HsPNP:Gua complex, PNP apoenzyme, and, HsPNP:immucillin-H provides explanation for inhibitor binding, refines the, purine-binding site, and can be used for future inhibitor design.
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<StructureSection load='1v2h' size='340' side='right'caption='[[1v2h]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1v2h]] 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=1V2H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1V2H 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]] 2.7&#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=GUN:GUANINE'>GUN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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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=1v2h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1v2h OCA], [https://pdbe.org/1v2h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1v2h RCSB], [https://www.ebi.ac.uk/pdbsum/1v2h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1v2h 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/v2/1v2h_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=1v2h 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 (PNP) catalyzes the phosphorolysis of the N-ribosidic bonds of purine nucleosides and deoxynucleosides. PNP is a target for inhibitor development aiming at T-cell immune response modulation and has been submitted to extensive structure-based drug design. More recently, the 3-D structure of human PNP has been refined to 2.3A resolution, which allowed a redefinition of the residues involved in the substrate-binding sites and provided a more reliable model for structure-based design of inhibitors. This work reports crystallographic study of the complex of Human PNP:guanine (HsPNP:Gua) solved at 2.7A resolution using synchrotron radiation. Analysis of the structural differences among the HsPNP:Gua complex, PNP apoenzyme, and HsPNP:immucillin-H provides explanation for inhibitor binding, refines the purine-binding site, and can be used for future inhibitor design.
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==Disease==
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Crystal structure of human PNP complexed with guanine.,de Azevedo WF Jr, Canduri F, dos Santos DM, Pereira JH, Bertacine Dias MV, Silva RG, Mendes MA, Basso LA, Palma MS, Santos DS Biochem Biophys Res Commun. 2003 Dec 19;312(3):767-72. PMID:14680831<ref>PMID:14680831</ref>
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Known diseases associated with this structure: Neutral lipid storage disease with myopathy OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=609059 609059]], Nucleoside phosphorylase deficiency, immunodeficiency due to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164050 164050]]
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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1V2H is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=GUN:'>GUN</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Purine-nucleoside_phosphorylase Purine-nucleoside phosphorylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.1 2.4.2.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1V2H OCA].
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</div>
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<div class="pdbe-citations 1v2h" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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Crystal structure of human PNP complexed with guanine., de Azevedo WF Jr, Canduri F, dos Santos DM, Pereira JH, Bertacine Dias MV, Silva RG, Mendes MA, Basso LA, Palma MS, Santos DS, Biochem Biophys Res Commun. 2003 Dec 19;312(3):767-72. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=14680831 14680831]
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*[[Purine nucleoside phosphorylase|Purine nucleoside phosphorylase]]
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*[[Purine nucleoside phosphorylase 3D structures|Purine nucleoside phosphorylase 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[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: Single protein]]
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[[Category: Basso LA]]
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[[Category: Basso, L.A.]]
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[[Category: Bertacine Dias MV]]
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[[Category: Canduri, F.]]
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[[Category: Canduri F]]
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[[Category: Dias, M.V.Bertacine.]]
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[[Category: De Azevedo Jr WF]]
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[[Category: Jr., W.F.De.Azevedo.]]
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[[Category: Dos Santos DM]]
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[[Category: Palma, M.S.]]
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[[Category: Palma MS]]
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[[Category: Pereira, J.H.]]
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[[Category: Pereira JH]]
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[[Category: Santos, D.M.Dos.]]
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[[Category: Santos DS]]
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[[Category: Santos, D.S.]]
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[[Category: Silva RG]]
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[[Category: Silva, R.G.]]
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[[Category: GUN]]
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[[Category: SO4]]
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[[Category: crystallography]]
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[[Category: drug design]]
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[[Category: guanine]]
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[[Category: purine nucleoside phosphorylase]]
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[[Category: synchrotron]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 17:04:11 2008''
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Current revision

Crystal structure of human PNP complexed with guanine

PDB ID 1v2h

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