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==Cryo-EM structure of two abaucin-bound LolDF in Acinetobacter baumannii== | |||
<StructureSection load='9w2w' size='340' side='right'caption='[[9w2w]], [[Resolution|resolution]] 3.50Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[9w2w]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Acinetobacter_baumannii Acinetobacter baumannii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9W2W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9W2W 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]] 3.5Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=R6Q:1-[2-[4-(trifluoromethyl)phenyl]ethyl]spiro[1~{H}-3,1-benzoxazine-4,4-piperidine]-2-one'>R6Q</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=9w2w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9w2w OCA], [https://pdbe.org/9w2w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9w2w RCSB], [https://www.ebi.ac.uk/pdbsum/9w2w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9w2w ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The growing crisis of antimicrobial resistance demands urgent need for antibiotics with alternative targets and modes of action (MOAs). Lipoproteins play crucial roles in bacterial survival and immunoregulation. The lipoprotein transporter, known as LolCDE or LolDF, has recently emerged as an effective target for selectively killing pathogenic bacteria such as Acinetobacter baumannii while sparing gut microbiota. While the heterodimeric LolCDE in Escherichia coli has been extensively studied, the druggable pocket and structural dynamics of the distinct homodimeric LolDF that exists in many critical pathogens are poorly understood. Such a knowledge gap limits our ability to exploit the Lol system to develop drugs with desired spectra of antibacterial activity. Here we determine the cryo-EM structures of homodimeric LolDF of A. baumannii in nucleotide-free apo-closed, vanadate-trapped fully closed, and inhibitor-bound open conformations, revealing the distinct structural features and conformational cycle of LolDF. Further cryo-EM, biochemical and functional analyses uncover the MOA of abaucin, a recently identified LolDF-targeting compound, demonstrating how multiple abaucin molecules open LolDF in a stepwise manner to establish an induced-fit pocket. Together, our results advance the understanding of LolDF function and inhibition, and provide the cryptic druggable conformation and specific inhibitor-bound pocket for structure-based drug discovery to target the dynamic lipoprotein transporter in A. baumannii. | |||
Structure and druggable conformation of the homodimeric lipoprotein transporter of Acinetobacter baumannii.,Zhang S, Tang Z, Shi W, Su J, Che C, Xing Q, Liao M, Li Y Nat Commun. 2026 May 6. doi: 10.1038/s41467-026-72778-x. PMID:42091888<ref>PMID:42091888</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 9w2w" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Acinetobacter baumannii]] | |||
[[Category: Large Structures]] | |||
[[Category: Li Y]] | |||
[[Category: Liao M]] | |||
[[Category: Zhang S]] | |||
