8hsy: Difference between revisions

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-'''Unreleased structure'''
-The entry 8hsy is ON HOLD
+==Acyl-ACP Synthetase structure==
+<StructureSection load='8hsy' size='340' side='right'caption='[[8hsy]], [[Resolution|resolution]] 2.53&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8hsy]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Vibrio_harveyi Vibrio harveyi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8HSY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8HSY FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.53&#8491;</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=8hsy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8hsy OCA], [https://pdbe.org/8hsy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8hsy RCSB], [https://www.ebi.ac.uk/pdbsum/8hsy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8hsy ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/Q00IB3_VIBHA Q00IB3_VIBHA]
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Antimicrobial resistance is an ongoing "one health" challenge of global concern. The acyl-ACP synthetase (termed AasS) of the zoonotic pathogen Vibrio harveyi recycles exogenous fatty acid (eFA), bypassing the requirement of type II fatty acid synthesis (FAS II), a druggable pathway. A growing body of bacterial AasS-type isoenzymes compromises the clinical efficacy of FAS II-directed antimicrobials, like cerulenin. Very recently, an acyl adenylate mimic, C10-AMS, was proposed as a lead compound against AasS activity. However, the underlying mechanism remains poorly understood. Here we present two high-resolution cryo-EM structures of AasS liganded with C10-AMS inhibitor (2.33 A) and C10-AMP intermediate (2.19 A) in addition to its apo form (2.53 A). Apart from our measurements for C10-AMS' Ki value of around 0.6 muM, structural and functional analyses explained how this inhibitor interacts with AasS enzyme. Unlike an open state of AasS, ready for C10-AMP formation, a closed conformation is trapped by the C10-AMS inhibitor. Tight binding of C10-AMS blocks fatty acyl substrate entry, and therefore inhibits AasS action. Additionally, this intermediate analog C10-AMS appears to be a mixed-type AasS inhibitor. In summary, our results provide the proof of principle that inhibiting salvage of eFA by AasS reverses the FAS II bypass. This facilitates the development of next-generation anti-bacterial therapeutics, esp. the dual therapy consisting of C10-AMS scaffold derivatives combined with certain FAS II inhibitors.
-Authors:
+An inhibitory mechanism of AasS, an exogenous fatty acid scavenger: Implications for re-sensitization of FAS II antimicrobials.,Huang H, Chang S, Cui T, Huang M, Qu J, Zhang H, Lu T, Zhang X, Zhou C, Feng Y PLoS Pathog. 2024 Jul 15;20(7):e1012376. doi: 10.1371/journal.ppat.1012376. , eCollection 2024 Jul. PMID:39008531<ref>PMID:39008531</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 8hsy" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Vibrio harveyi]]
+[[Category: Chang S]]
+[[Category: Cui T]]
+[[Category: Feng Y]]
+[[Category: Huang H]]
+[[Category: Wang C]]
+[[Category: Xu Y]]
+[[Category: Zhang H]]
+[[Category: Zhang X]]
+[[Category: Zhou C]]