7k13: Difference between revisions
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New page: '''Unreleased structure''' The entry 7k13 is ON HOLD Authors: Yang, Y., Liu, A. Description: ACMSD in complex with diflunisal derivative 14 Category: Unreleased Structures [[Catego... |
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==ACMSD in complex with diflunisal derivative 14== | |||
<StructureSection load='7k13' size='340' side='right'caption='[[7k13]], [[Resolution|resolution]] 1.83Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7k13]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_fluorescens Pseudomonas fluorescens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7K13 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7K13 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]] 1.83Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=VR7:2-hydroxy-5-(thiophen-3-yl)benzoic+acid'>VR7</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=7k13 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7k13 OCA], [https://pdbe.org/7k13 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7k13 RCSB], [https://www.ebi.ac.uk/pdbsum/7k13 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7k13 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q83V25_PSEFL Q83V25_PSEFL] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
In the kynurenine pathway for tryptophan degradation, an unstable metabolic intermediate, alpha-amino-beta-carboxymuconate-epsilon-semialdehyde (ACMS), can nonenzymatically cyclize to form quinolinic acid, the precursor for de novo biosynthesis of nicotinamide adenine dinucleotide (NAD(+)). In a competing reaction, ACMS is decarboxylated by ACMS decarboxylase (ACMSD) for further metabolism and energy production. Therefore, the inhibition of ACMSD increases NAD(+) levels. In this study, an Food and Drug Administration (FDA)-approved drug, diflunisal, was found to competitively inhibit ACMSD. The complex structure of ACMSD with diflunisal revealed a previously unknown ligand-binding mode and was consistent with the results of inhibition assays, as well as a structure-activity relationship (SAR) study. Moreover, two synthesized diflunisal derivatives showed half-maximal inhibitory concentration (IC50) values 1 order of magnitude better than diflunisal at 1.32 +/- 0.07 muM (22) and 3.10 +/- 0.11 muM (20), respectively. The results suggest that diflunisal derivatives have the potential to modulate NAD(+) levels. The ligand-binding mode revealed here provides a new direction for developing inhibitors of ACMSD. | |||
Diflunisal Derivatives as Modulators of ACMS Decarboxylase Targeting the Tryptophan-Kynurenine Pathway.,Yang Y, Borel T, de Azambuja F, Johnson D, Sorrentino JP, Udokwu C, Davis I, Liu A, Altman RA J Med Chem. 2020 Dec 28. doi: 10.1021/acs.jmedchem.0c01762. PMID:33369426<ref>PMID:33369426</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 7k13" style="background-color:#fffaf0;"></div> | ||
[[Category: Liu | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Pseudomonas fluorescens]] | |||
[[Category: Liu A]] | |||
[[Category: Yang Y]] | |||
Latest revision as of 15:15, 18 October 2023
ACMSD in complex with diflunisal derivative 14
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