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| | ==The crystal structure of human quinolinic acid phosphoribosyltransferase in complex with its inhibitor phthalic acid== | | ==The crystal structure of human quinolinic acid phosphoribosyltransferase in complex with its inhibitor phthalic acid== |
| - | <StructureSection load='4kww' size='340' side='right' caption='[[4kww]], [[Resolution|resolution]] 2.55Å' scene=''> | + | <StructureSection load='4kww' size='340' side='right'caption='[[4kww]], [[Resolution|resolution]] 2.55Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4kww]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KWW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4KWW FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4kww]] 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=4KWW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4KWW FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PHT:PHTHALIC+ACID'>PHT</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PHT:PHTHALIC+ACID'>PHT</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4kwv|4kwv]]</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=4kww FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kww OCA], [https://pdbe.org/4kww PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4kww RCSB], [https://www.ebi.ac.uk/pdbsum/4kww PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4kww ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">QPRT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Nicotinate-nucleotide_diphosphorylase_(carboxylating) Nicotinate-nucleotide diphosphorylase (carboxylating)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.19 2.4.2.19] </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=4kww FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kww OCA], [http://pdbe.org/4kww PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4kww RCSB], [http://www.ebi.ac.uk/pdbsum/4kww PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4kww ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/NADC_HUMAN NADC_HUMAN]] Involved in the catabolism of quinolinic acid (QA).<ref>PMID:17868694</ref> | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Phosphoribosyltransferase|Phosphoribosyltransferase]] | + | *[[Phosphoribosyltransferase 3D structures|Phosphoribosyltransferase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Dimeka, P N]] | + | [[Category: Large Structures]] |
| - | [[Category: Malik, S S]] | + | [[Category: Dimeka PN]] |
| - | [[Category: Ncube, Z]] | + | [[Category: Malik SS]] |
| - | [[Category: Toth, E A]] | + | [[Category: Ncube Z]] |
| - | [[Category: Brain]] | + | [[Category: Toth EA]] |
| - | [[Category: Metabolism]]
| + | |
| - | [[Category: Nad]]
| + | |
| - | [[Category: Prpp]]
| + | |
| - | [[Category: Quinolinic acid]]
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| - | [[Category: Transferase-transferase inhibitor complex]]
| + | |
| - | [[Category: Type ii phosphoribosyltransferase]]
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| Structural highlights
Function
NADC_HUMAN Involved in the catabolism of quinolinic acid (QA).[1]
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Liu H, Woznica K, Catton G, Crawford A, Botting N, Naismith JH. Structural and kinetic characterization of quinolinate phosphoribosyltransferase (hQPRTase) from homo sapiens. J Mol Biol. 2007 Oct 26;373(3):755-63. Epub 2007 Aug 24. PMID:17868694 doi:10.1016/j.jmb.2007.08.043
- ↑ Malik SS, Patterson DN, Ncube Z, Toth EA. The crystal structure of human quinolinic acid phosphoribosyltransferase in complex with its inhibitor phthalic acid. Proteins. 2013 Aug 28. doi: 10.1002/prot.24406. PMID:24038671 doi:10.1002/prot.24406
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