View source for 5ugf


==Crystal structure of human purine nucleoside phosphorylase (F159Y) mutant complexed with DADMe-ImmG and phosphate==
<StructureSection load='5ugf' size='340' side='right'caption='[[5ugf]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5ugf]] is a 6 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=5UGF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5UGF 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]] 2.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=5ugf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ugf OCA], [https://pdbe.org/5ugf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ugf RCSB], [https://www.ebi.ac.uk/pdbsum/5ugf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ugf 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 ==
Heavy-enzyme isotope effects (15N-, 13C-, and 2H-labeled protein) explore mass-dependent vibrational modes linked to catalysis. Transition path-sampling (TPS) calculations have predicted femtosecond dynamic coupling at the catalytic site of human purine nucleoside phosphorylase (PNP). Coupling is observed in heavy PNPs, where slowed barrier crossing caused a normal heavy-enzyme isotope effect (kchemlight/kchemheavy &gt; 1.0). We used TPS to design mutant F159Y PNP, predicted to improve barrier crossing for heavy F159Y PNP, an attempt to generate a rare inverse heavy-enzyme isotope effect (kchemlight/kchemheavy &lt; 1.0). Steady-state kinetic comparison of light and heavy native PNPs to light and heavy F159Y PNPs revealed similar kinetic properties. Pre-steady-state chemistry was slowed 32-fold in F159Y PNP. Pre-steady-state chemistry compared heavy and light native and F159Y PNPs and found a normal heavy-enzyme isotope effect of 1.31 for native PNP and an inverse effect of 0.75 for F159Y PNP. Increased isotopic mass in F159Y PNP causes more efficient transition state formation. Independent validation of the inverse isotope effect for heavy F159Y PNP came from commitment to catalysis experiments. Most heavy enzymes demonstrate normal heavy-enzyme isotope effects, and F159Y PNP is a rare example of an inverse effect. Crystal structures and TPS dynamics of native and F159Y PNPs explore the catalytic-site geometry associated with these catalytic changes. Experimental validation of TPS predictions for barrier crossing establishes the connection of rapid protein dynamics and vibrational coupling to enzymatic transition state passage.

Catalytic-site design for inverse heavy-enzyme isotope effects in human purine nucleoside phosphorylase.,Harijan RK, Zoi I, Antoniou D, Schwartz SD, Schramm VL Proc Natl Acad Sci U S A. 2017 Jun 20;114(25):6456-6461. doi:, 10.1073/pnas.1704786114. Epub 2017 Jun 5. PMID:28584087<ref>PMID:28584087</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5ugf" style="background-color:#fffaf0;"></div>

==See Also==
*[[Purine nucleoside phosphorylase 3D structures|Purine nucleoside phosphorylase 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Almo SC]]
[[Category: Bonanno JB]]
[[Category: Cameron SA]]
[[Category: Harijan RK]]
[[Category: Schramm VL]]