View source for 5ayz


==CRYSTAL STRUCTURE OF HUMAN QUINOLINATE PHOSPHORIBOSYLTRANSFERASE IN COMPLEX WITH THE PRODUCT NICOTINATE MONONUCLEOTIDE==
<StructureSection load='5ayz' size='340' side='right'caption='[[5ayz]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5ayz]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4r3y 4r3y]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AYZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5AYZ 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]] 2.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NCN:NICOTINATE+MONONUCLEOTIDE'>NCN</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=5ayz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ayz OCA], [https://pdbe.org/5ayz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ayz RCSB], [https://www.ebi.ac.uk/pdbsum/5ayz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ayz ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/NADC_HUMAN NADC_HUMAN] Involved in the catabolism of quinolinic acid (QA).<ref>PMID:17868694</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Quinolinate phosphoribosyltransferase (QPRT) catalyses the production of nicotinic acid mononucleotide, a precursor of de novo biosynthesis of the ubiquitous coenzyme nicotinamide adenine dinucleotide. QPRT is also essential for maintaining the homeostasis of quinolinic acid in the brain, a possible neurotoxin causing various neurodegenerative diseases. Although QPRT has been extensively analysed, the molecular basis of the reaction catalysed by human QPRT remains unclear. Here, we present the crystal structures of hexameric human QPRT in the apo form and its complexes with reactant or product. We found that the interaction between dimeric subunits was dramatically altered during the reaction process by conformational changes of two flexible loops in the active site at the dimer-dimer interface. In addition, the N-terminal short helix alpha1 was identified as a critical hexamer stabilizer. The structural features, size distribution, heat aggregation and ITC studies of the full-length enzyme and the enzyme lacking helix alpha1 strongly suggest that human QPRT acts as a hexamer for cooperative reactant binding via three dimeric subunits and maintaining stability. Based on our comparison of human QPRT structures in the apo and complex forms, we propose a drug design strategy targeting malignant glioma.

Structural Insights into the Quaternary Catalytic Mechanism of Hexameric Human Quinolinate Phosphoribosyltransferase, a Key Enzyme in de novo NAD Biosynthesis.,Youn HS, Gyun Kim T, Kim MK, Bu Kang G, Youn Kang J, Lee JG, Yop An J, Ryoung Park K, Lee Y, Jun Im Y, Hyuck Lee J, Hyun Eom S Sci Rep. 2016 Jan 25;6:19681. doi: 10.1038/srep19681. PMID:26805589<ref>PMID:26805589</ref>

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

==See Also==
*[[Phosphoribosyltransferase 3D structures|Phosphoribosyltransferase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: An JY]]
[[Category: Eom SH]]
[[Category: Fukuoka SI]]
[[Category: Im YJ]]
[[Category: Kang GB]]
[[Category: Kang JY]]
[[Category: Kim MK]]
[[Category: Kim TG]]
[[Category: Lee JG]]
[[Category: Lee JH]]
[[Category: Lee Y]]
[[Category: Park KR]]
[[Category: Seo YJ]]
[[Category: Youn HS]]