View source for 6fch


==Crystal Structure of Human APRT wild type in complex with PRPP and Mg2+==
<StructureSection load='6fch' size='340' side='right' caption='[[6fch]], [[Resolution|resolution]] 1.45&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6fch]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FCH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FCH FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PRP:ALPHA-PHOSPHORIBOSYLPYROPHOSPHORIC+ACID'>PRP</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5hnd|5hnd]], [[6fci|6fci]], [[6fcl|6fcl]], [[6fd4|6fd4]], [[6fd5|6fd5]], [[6fd6|6fd6]]</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Adenine_phosphoribosyltransferase Adenine phosphoribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.7 2.4.2.7] </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=6fch FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fch OCA], [http://pdbe.org/6fch PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fch RCSB], [http://www.ebi.ac.uk/pdbsum/6fch PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fch ProSAT]</span></td></tr>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/APT_HUMAN APT_HUMAN]] Defects in APRT are the cause of adenine phosphoribosyltransferase deficiency (APRTD) [MIM:[http://omim.org/entry/614723 614723]]; also known as 2,8-dihydroxyadenine urolithiasis. An enzymatic deficiency that can lead to urolithiasis and renal failure. Patients have 2,8-dihydroxyadenine (DHA) urinary stones.<ref>PMID:1746557</ref> <ref>PMID:7915931</ref> <ref>PMID:3680503</ref> <ref>PMID:3343350</ref> <ref>PMID:1353080</ref> <ref>PMID:11243733</ref> <ref>PMID:15571218</ref> <ref>PMID:21635362</ref>  
== Function ==
[[http://www.uniprot.org/uniprot/APT_HUMAN APT_HUMAN]] Catalyzes a salvage reaction resulting in the formation of AMP, that is energically less costly than de novo synthesis. 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Phosphoribosyltransferases catalyze the displacement of a PRPP alpha-1'-pyrophosphate to a nitrogen-containing nucleobase. How they control the balance of substrates/products binding and activities is poorly understood. Here, we investigated the human adenine phosphoribosyltransferase (hAPRT) that produces AMP in the purine salvage pathway. We show that a single oxygen atom from the Tyr105 side chain is responsible for selecting the active conformation of the 12 amino acid long catalytic loop. Using in vitro, cellular, and in crystallo approaches, we demonstrated that Tyr105 is key for the fine-tuning of the kinetic activity efficiencies of the forward and reverse reactions. Together, our results reveal an evolutionary pressure on the strictly conserved Tyr105 and on the dynamic motion of the flexible loop in phosphoribosyltransferases that is essential for purine biosynthesis in cells. These data also provide the framework for designing novel adenine derivatives that could modulate, through hAPRT, diseases-involved cellular pathways.

Structural Insights into the Forward and Reverse Enzymatic Reactions in Human Adenine Phosphoribosyltransferase.,Huyet J, Ozeir M, Burgevin MC, Pinson B, Chesney F, Remy JM, Siddiqi AR, Lupoli R, Pinon G, Saint-Marc C, Gibert JF, Morales R, Ceballos-Picot I, Barouki R, Daignan-Fornier B, Olivier-Bandini A, Auge F, Nioche P Cell Chem Biol. 2018 Jun 21;25(6):666-676.e4. doi:, 10.1016/j.chembiol.2018.02.011. Epub 2018 Mar 22. PMID:29576532<ref>PMID:29576532</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6fch" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Adenine phosphoribosyltransferase]]
[[Category: Huyet, J]]
[[Category: Nioche, P]]
[[Category: Ozeir, M]]
[[Category: Rossmann fold]]
[[Category: Transferase]]