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9lww
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of dehydrogenase/isomerase FabX from Helicobacter pylori in complex with inhibitor 47== | |
| + | <StructureSection load='9lww' size='340' side='right'caption='[[9lww]], [[Resolution|resolution]] 1.70Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[9lww]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Helicobacter_pylori Helicobacter pylori]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9LWW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9LWW 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]] 1.7Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1EMD:~{N}-[5-[[3-(dimethylamino)phenyl]sulfamoyl]-1,3,4-thiadiazol-2-yl]naphthalene-2-carboxamide'>A1EMD</scene>, <scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</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=9lww FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9lww OCA], [https://pdbe.org/9lww PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9lww RCSB], [https://www.ebi.ac.uk/pdbsum/9lww PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9lww ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/A0A0B2E3F3_HELPX A0A0B2E3F3_HELPX] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Unsaturated fatty acids (UFAs) are essential for the membrane function in most bacteria. In Helicobacter pylori (H. pylori), a gastric pathogen, UFA biosynthesis depends on the bifunctional dehydrogenase/isomerase FabX, a promising target against H. pylori. Herein, we report the first FabX inhibitor, P61G11 (compound 1, IC(50) = 3.7 +/- 0.2 muM), identified via high-throughput screening and featuring a 1,3,4-thiadiazole sulfonamide scaffold. The costructure of FabX-1 reveals occupancy of the L-shaped substrate-binding tunnel via hydrophobic interactions and hydrogen bonds. Structure-based optimization led to more potent derivatives, among which compound 47 showed potent inhibition (IC(50) = 0.128 +/- 0.002 muM), representing a 29-fold improvement. Compound 47 also demonstrated strong in vitro antibacterial activity (MIC = 0.5-1 mug/mL), when combined with membrane permeabilizers, efflux pump inhibitors, and clarithromycin, and exhibited narrow-spectrum efficacy against H. pylori, providing a novel strategy for anti-H. pylori therapy. | ||
| - | + | Discovery of 1,3,4-Thiadiazole Sulfonamide-Based Potent Inhibitors against the Unsaturated Fatty Acid Synthase FabX of Helicobacter pylori.,Ruan X, Zhang L, Dong L, Wang Y, Zeng L, Yang M, Bi H, Feng M, Zhang L, Zhou L J Med Chem. 2025 Aug 28;68(16):17175-17188. doi: 10.1021/acs.jmedchem.5c00654. , Epub 2025 Aug 14. PMID:40811148<ref>PMID:40811148</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 9lww" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Helicobacter pylori]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Zhang L]] | ||
Current revision
Crystal structure of dehydrogenase/isomerase FabX from Helicobacter pylori in complex with inhibitor 47
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