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| | <StructureSection load='6or8' size='340' side='right'caption='[[6or8]], [[Resolution|resolution]] 1.65Å' scene=''> | | <StructureSection load='6or8' size='340' side='right'caption='[[6or8]], [[Resolution|resolution]] 1.65Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6or8]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Pyrococcus_horikoshii Pyrococcus horikoshii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OR8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6OR8 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6or8]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Pyrococcus_horikoshii_OT3 Pyrococcus horikoshii OT3]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OR8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6OR8 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5XR:2-hydroxy-N-[(1S)-1-hydroxy-3-oxopropyl]-L-aspartic+acid'>5XR</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=SF4:IRON/SULFUR+CLUSTER'>SF4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.65Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5ffk|5ffk]], [[5fev|5fev]], [[5feu|5feu]], [[4zkz|4zkz]], [[4zk6|4zk6]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5XR:2-hydroxy-N-[(1S)-1-hydroxy-3-oxopropyl]-L-aspartic+acid'>5XR</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=SF4:IRON/SULFUR+CLUSTER'>SF4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">nadA, PH0013 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=70601 Pyrococcus horikoshii])</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=6or8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6or8 OCA], [https://pdbe.org/6or8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6or8 RCSB], [https://www.ebi.ac.uk/pdbsum/6or8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6or8 ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Quinolinate_synthase Quinolinate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.72 2.5.1.72] </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=6or8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6or8 OCA], [http://pdbe.org/6or8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6or8 RCSB], [http://www.ebi.ac.uk/pdbsum/6or8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6or8 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/NADA_PYRHO NADA_PYRHO]] Catalyzes the condensation of iminoaspartate with dihydroxyacetone phosphate to form quinolinate (By similarity). | + | [https://www.uniprot.org/uniprot/NADA_PYRHO NADA_PYRHO] Catalyzes the condensation of iminoaspartate with dihydroxyacetone phosphate to form quinolinate (By similarity). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Pyrococcus horikoshii]] | + | [[Category: Pyrococcus horikoshii OT3]] |
| - | [[Category: Quinolinate synthase]]
| + | [[Category: Booker SJ]] |
| - | [[Category: Booker, S J]] | + | [[Category: Esakova OA]] |
| - | [[Category: Esakova, O A]] | + | [[Category: Grove TL]] |
| - | [[Category: Grove, T L]] | + | [[Category: Yennawar NH]] |
| - | [[Category: Yennawar, N H]] | + | |
| - | [[Category: Biosynthesis of nicotinamide adenine dinucleotide]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
NADA_PYRHO Catalyzes the condensation of iminoaspartate with dihydroxyacetone phosphate to form quinolinate (By similarity).
Publication Abstract from PubMed
Quinolinic acid (QA) is a common intermediate in the biosynthesis of nicotinamide adenine dinucleotide (NAD+) and its derivatives in all organisms that synthesize the molecule de novo. In most prokaryotes, it is formed from the condensation of dihydroxyacetone phosphate (DHAP) and iminoaspartate (IA) by the action of quinolinate synthase (NadA). NadA contains a [4Fe-4S] cluster cofactor with a unique non-cysteinyl-ligated iron ion (Fea), which is proposed to bind the hydroxyl group of an intermediate in its reaction to facilitate a dehydration step. However, direct evidence for this role in catalysis has yet to be provided, and the exact chemical mechanism that underlies this transformation remains elusive. Herein, we present a structure of NadA from Pyrococcus horikoshii (PhNadA) in complex with IA and show that a carboxylate group of the molecule is ligated to Fea of the iron-sulfur cluster, occupying the site to which DHAP has been proposed to bind during catalysis. When crystals of PhNadA in complex with IA are soaked briefly in DHAP before freezing, electron density for a new molecule is observed, which we suggest is related to an intermediate in the reaction. Similar, but slightly different "intermediates" are observed when crystals of a PhNadA Glu198Gln variant are incubated with DHAP, oxaloacetate, and ammonium chloride, conditions under which IA is formed chemically. Continuous-wave and pulse electron paramagnetic resonance techniques are used to verify the binding mode of substrates and proposed intermediates in frozen solution.
An Unexpected Species Determined by X-ray Crystallography that May Represent an Intermediate in the Reaction Catalyzed by Quinolinate Synthase.,Esakova OA, Silakov A, Grove TL, Warui DM, Yennawar NH, Booker SJ J Am Chem Soc. 2019 Aug 7. doi: 10.1021/jacs.9b02513. PMID:31390192[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Esakova OA, Silakov A, Grove TL, Warui DM, Yennawar NH, Booker SJ. An Unexpected Species Determined by X-ray Crystallography that May Represent an Intermediate in the Reaction Catalyzed by Quinolinate Synthase. J Am Chem Soc. 2019 Aug 7. doi: 10.1021/jacs.9b02513. PMID:31390192 doi:http://dx.doi.org/10.1021/jacs.9b02513
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