View source for 4ear


==Crystal structure of purine nucleoside phosphorylase (W16Y, W94Y, W178Y, H257W) mutant from human complexed with DADMe-ImmG and phosphate==
<StructureSection load='4ear' size='340' side='right'caption='[[4ear]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4ear]] is a 3 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=4EAR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EAR 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]] 1.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FT6:6-FLUORO-L-TRYPTOPHAN'>FT6</scene>, <scene name='pdbligand=IM5:2-AMINO-7-{[(3R,4R)-3-HYDROXY-4-(HYDROXYMETHYL)PYRROLIDIN-1-YL]METHYL}-3,5-DIHYDRO-4H-PYRROLO[3,2-D]PYRIMIDIN-4-ONE'>IM5</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=4ear FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ear OCA], [https://pdbe.org/4ear PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ear RCSB], [https://www.ebi.ac.uk/pdbsum/4ear PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ear 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> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Purine nucleoside phosphorylase (PNP) is a target for leukemia, gout, and autoimmune disorders. Dynamic motion of catalytic site loops has been implicated in catalysis, but experimental evidence was lacking. We replaced catalytic site groups His257 or His64 with 6-fluoro-tryptophan (6FW) as site-specific NMR probes. Conformational adjustments in the 6FW-His257-helical and His64-6FW-loop regions were characterized in PNP phosphate-bound enzyme and in complexes with catalytic site ligands, including transition state analogs. Chemical shift and line-shape changes associated with these complexes revealed dynamic coexistence of several conformational states in these regions in phosphate-bound enzyme and altered or single conformations in other complexes. These conformations were also characterized by X-ray crystallography. Specific (19)F-Trp labels and X-ray crystallography provide multidimensional characterization of conformational states for free, catalytic, and inhibited complexes of human PNP.

Catalytic Site Conformations in Human PNP by (19)F-NMR and Crystallography.,Suarez J, Haapalainen AM, Cahill SM, Ho MC, Yan F, Almo SC, Schramm VL Chem Biol. 2013 Feb 21;20(2):212-22. doi: 10.1016/j.chembiol.2013.01.009. PMID:23438750<ref>PMID:23438750</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4ear" style="background-color:#fffaf0;"></div>

==See Also==
*[[Purine nucleoside phosphorylase 3D structures|Purine nucleoside phosphorylase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Almo SC]]
[[Category: Haapalainen AM]]
[[Category: Ho MC]]
[[Category: Schramm VL]]
[[Category: Suarez JJ]]