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{{STRUCTURE_4ece|  PDB=4ece  |  SCENE=  }}
==Crystal structure of purine nucleoside phosphorylase (W16Y, W94Y, W178Y, H257W) mutant from human complexed with guanine==
===Crystal structure of purine nucleoside phosphorylase (W16Y, W94Y, W178Y, H257W) mutant from human complexed with guanine===
<StructureSection load='4ece' size='340' side='right' caption='[[4ece]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
{{ABSTRACT_PUBMED_23438750}}
== Structural highlights ==
<table><tr><td colspan='2'>[[4ece]] is a 6 chain structure with 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=4ECE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ECE FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GUN:GUANINE'>GUN</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ear|4ear]], [[4eb8|4eb8]]</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NP, PNP, X00737.1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ece FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ece OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ece RCSB], [http://www.ebi.ac.uk/pdbsum/4ece PDBsum]</span></td></tr>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/PNPH_HUMAN PNPH_HUMAN]] Defects in PNP are the cause of purine nucleoside phosphorylase deficiency (PNPD) [MIM:[http://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 ==
[[http://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.


==About this Structure==
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>
[[4ece]] is a 6 chain structure with 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=4ECE OCA].
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
 
==See Also==
*[[Purine nucleoside phosphorylase|Purine nucleoside phosphorylase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Purine-nucleoside phosphorylase]]
[[Category: Purine-nucleoside phosphorylase]]
[[Category: Almo, S C.]]
[[Category: Almo, S C]]
[[Category: Haapalainen, A M.]]
[[Category: Haapalainen, A M]]
[[Category: Ho, M C.]]
[[Category: Ho, M C]]
[[Category: Schramm, V L.]]
[[Category: Schramm, V L]]
[[Category: Suarez, J J.]]
[[Category: Suarez, J J]]
[[Category: Cytosol]]
[[Category: Cytosol]]
[[Category: Drug binding]]
[[Category: Drug binding]]

Revision as of 11:37, 18 December 2014

Crystal structure of purine nucleoside phosphorylase (W16Y, W94Y, W178Y, H257W) mutant from human complexed with guanineCrystal structure of purine nucleoside phosphorylase (W16Y, W94Y, W178Y, H257W) mutant from human complexed with guanine

Structural highlights

4ece is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:NP, PNP, X00737.1 (Homo sapiens)
Activity:Purine-nucleoside phosphorylase, with EC number 2.4.2.1
Resources:FirstGlance, OCA, RCSB, PDBsum

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]

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[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ 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
  2. ↑ 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
  3. ↑ 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
  4. ↑ 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
  5. ↑ Suarez J, Haapalainen AM, Cahill SM, Ho MC, Yan F, Almo SC, Schramm VL. Catalytic Site Conformations in Human PNP by (19)F-NMR and Crystallography. Chem Biol. 2013 Feb 21;20(2):212-22. doi: 10.1016/j.chembiol.2013.01.009. PMID:23438750 doi:http://dx.doi.org/10.1016/j.chembiol.2013.01.009

4ece, resolution 2.60Å

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