4kwv: Difference between revisions
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==Crystal Structure of human apo-QPRT== | |||
<StructureSection load='4kwv' size='340' side='right'caption='[[4kwv]], [[Resolution|resolution]] 2.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4kwv]] 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=4KWV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4KWV 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]] 2.797Å</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=4kwv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kwv OCA], [https://pdbe.org/4kwv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4kwv RCSB], [https://www.ebi.ac.uk/pdbsum/4kwv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4kwv 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 == | |||
Quinolinic acid (QA), a biologically potent but neurodestructive metabolite is catabolized by quinolinic acid phosphoribosyltransferase (QPRT) in the first step of the de novo NAD+ biosynthesis pathway. This puts QPRT at the junction of two different pathways i.e. de novo NAD+ biosynthesis and the kynurenine pathway of tryptophan degradation. Thus, QPRT is an important enzyme in terms of its biological impact and its potential as a therapeutic target. Here we report the crystal structure of human QPRT bound to its inhibitor phthalic acid (PHT) and kinetic analysis of PHT inhibition of human QPRT. This structure, determined at 2.55 A resolution, shows an elaborate hydrogen bonding network that helps in recognition of PHT and consequently its substrate QA. In addition to this hydrogen bonding network, we observe extensive van der Waals contacts with the PHT ring that might be important for correctly orientating the substrate QA during catalysis. Moreover, our crystal form allows us to observe an intact hexamer in both the apo- and PHT-bound forms in the same crystal system, which provides a direct comparison of unique subunit interfaces formed in hexameric human QPRT. We call these interfaces "non-dimeric interfaces" to distinguish them from the typical dimeric interfaces observed in all QPRTs. We observe significant changes in the non-dimeric interfaces in the QPRT hexamer upon binding PHT. Thus, the new structural and functional features of this enzyme we describe here will aid in understanding the function of hexameric QPRTs, which includes all eukaryotic and select prokaryotic QPRTs. (c) Proteins 2013;. (c) 2013 Wiley Periodicals, Inc. | |||
The crystal structure of human quinolinic acid phosphoribosyltransferase in complex with its inhibitor phthalic acid.,Malik SS, Patterson DN, Ncube Z, Toth EA Proteins. 2013 Aug 28. doi: 10.1002/prot.24406. PMID:24038671<ref>PMID:24038671</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4kwv" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Phosphoribosyltransferase 3D structures|Phosphoribosyltransferase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Malik SS]] | |||
[[Category: Ncube Z]] | |||
[[Category: Patterson DN]] | |||
[[Category: Toth EA]] | |||