1m73

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
(New page: 200px<br /> <applet load="1m73" size="450" color="white" frame="true" align="right" spinBox="true" caption="1m73, resolution 2.3&Aring;" /> '''CRYSTAL STRUCTURE OF...)
Current revision (07:18, 25 October 2023) (edit) (undo)
 
(15 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:1m73.gif|left|200px]]<br />
 
-
<applet load="1m73" size="450" color="white" frame="true" align="right" spinBox="true"
 
-
caption="1m73, resolution 2.3&Aring;" />
 
-
'''CRYSTAL STRUCTURE OF HUMAN PNP AT 2.3A RESOLUTION'''<br />
 
-
==Overview==
+
==CRYSTAL STRUCTURE OF HUMAN PNP AT 2.3A RESOLUTION==
-
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.
+
<StructureSection load='1m73' size='340' side='right'caption='[[1m73]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
 +
== Structural highlights ==
 +
<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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</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='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>
 +
== 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>
 +
== 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>
 +
== Evolutionary Conservation ==
 +
[[Image:Consurf_key_small.gif|200px|right]]
 +
Check<jmol>
 +
<jmolCheckbox>
 +
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/m7/1m73_consurf.spt"</scriptWhenChecked>
 +
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
 +
<text>to colour the structure by Evolutionary Conservation</text>
 +
</jmolCheckbox>
 +
</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=1m73 ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== 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.
-
==Disease==
+
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<ref>PMID:12914785</ref>
-
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]]
+
-
==About this Structure==
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
1M73 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 SO4 as [http://en.wikipedia.org/wiki/ligand ligand]. 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1M73 OCA].
+
</div>
 +
<div class="pdbe-citations 1m73" style="background-color:#fffaf0;"></div>
-
==Reference==
+
==See Also==
-
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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12914785 12914785]
+
*[[Purine nucleoside phosphorylase 3D structures|Purine nucleoside phosphorylase 3D structures]]
 +
== References ==
 +
<references/>
 +
__TOC__
 +
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
-
[[Category: Purine-nucleoside phosphorylase]]
+
[[Category: Large Structures]]
-
[[Category: Single protein]]
+
[[Category: Basso LA]]
-
[[Category: Basso, L.A.]]
+
[[Category: Canduri F]]
-
[[Category: Canduri, F.]]
+
[[Category: De Azevedo Jr WF]]
-
[[Category: Jr., W.F.De.Azevedo.]]
+
[[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: SO4]]
+
-
[[Category: crystallography]]
+
-
[[Category: drug design]]
+
-
[[Category: purine nucleoside phosphorylase]]
+
-
[[Category: synchrotron]]
+
-
 
+
-
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 18:08:19 2007''
+

Current revision

CRYSTAL STRUCTURE OF HUMAN PNP AT 2.3A RESOLUTION

PDB ID 1m73

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1m73"
Personal tools