9f94
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Complex of phenazine biosynthesis enzyme PhzF with 2-amino-5-(3-hydroxyphenyl)benzoic acid== | |
| + | <StructureSection load='9f94' size='340' side='right'caption='[[9f94]], [[Resolution|resolution]] 1.32Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[9f94]] is a 1 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=9F94 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9F94 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]] 1.32Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1IAY:2-azanyl-5-(3-hydroxyphenyl)benzoic+acid'>A1IAY</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</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=9f94 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9f94 OCA], [https://pdbe.org/9f94 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9f94 RCSB], [https://www.ebi.ac.uk/pdbsum/9f94 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9f94 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/PHZF_PSEFL PHZF_PSEFL] Isomerase that catalyzes the condensation of two molecules of trans-2,3-dihydro-3-hydroxyanthranilic acid (DHHA) into the phenazine ring system. The final product is not yet known.<ref>PMID:19053436</ref> <ref>PMID:15545603</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The phenazine pyocyanin is an important virulence factor of the pathogen Pseudomonas aeruginosa, which is on the WHO list of antibiotic resistant "priority pathogens". In this study the isomerase PhzF, a key bacterial enzyme of the pyocyanin biosynthetic pathway, was investigated as a pathoblocker target. The aim of the pathoblocker strategy is to reduce the virulence of the pathogen without killing it, thus preventing the rapid development of resistance. Based on crystal structures of PhzF, derivatives of the inhibitor 3-hydroxyanthranilic acid were designed. Co-crystal structures of the synthesized derivatives with PhzF revealed spacial limitations of the binding pocket of PhzF in the closed conformation. In contrast, ligands aligned to the open conformation of PhzF provided more room for structural modifications. The intrinsic fluorescence of small 3-hydroxyanthranilic acid derivatives enabled direct affinity determinations using FRET assays. The analysis of structure-activity relationships showed that the carboxylic acid moiety is essential for binding to the target enzyme. The results of this study provide fundamental structural insights that will be useful for the design of PhzF-inhibitors. | ||
| - | + | Substrate-Based Ligand Design for Phenazine Biosynthesis Enzyme PhzF.,Baumgarten J, Schneider P, Thiemann M, Zimmermann M, Diederich C, Blankenfeldt W, Kunick C ChemMedChem. 2024 Aug 20:e202400466. doi: 10.1002/cmdc.202400466. PMID:39163032<ref>PMID:39163032</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 9f94" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Pseudomonas fluorescens]] | ||
| + | [[Category: Baumgarten J]] | ||
| + | [[Category: Blankenfeldt W]] | ||
| + | [[Category: Kunick C]] | ||
| + | [[Category: Schneider P]] | ||
Current revision
Complex of phenazine biosynthesis enzyme PhzF with 2-amino-5-(3-hydroxyphenyl)benzoic acid
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