View source for 9qot


==APH(2'')-IVa with an inhibitor==
<StructureSection load='9qot' size='340' side='right'caption='[[9qot]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9qot]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Enterococcus_casseliflavus Enterococcus casseliflavus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9QOT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9QOT 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]] 2.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1I8M:5-chloranyl-4-(1~{H}-1,2,3-triazol-4-yl)-1~{H}-pyrrolo[2,3-b]pyridine'>A1I8M</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</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=9qot FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9qot OCA], [https://pdbe.org/9qot PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9qot RCSB], [https://www.ebi.ac.uk/pdbsum/9qot PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9qot ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/O68183_ENTCA O68183_ENTCA] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Antibiotic resistance is rapidly emerging as one of the most critical health threats, with resistant microorganisms progressively diminishing the effectiveness of established antibiotics. As a result, the development of therapeutic approaches that effectively target resistant pathogens is of utmost importance. In this study, we developed inhibitors for APH(2")-IVa, a bacterial kinase conveying resistance to aminoglycoside antibiotics. Starting from a hit of a fragment-based screening, we explored the inhibitory motif by structure-based design, ultimately leading to a series of triazole analogues. Advanced analogues displayed promising ADME properties, emerging selectivity vs a panel of human kinases, permeability in both Gram-positive and Gram-negative bacteria, and a moderate antibiotic efficacy for clinical strains of P. aeruginosa. Taken together, our results suggest inhibition of bacterial kinases could be a promising option to reinstall the efficacy of aminoglycoside antibiotics.

Targeting bacterial kinases as a strategy to counteract antibiotic resistance.,Buffa V, Kowalewski J, Qi G, Deutscher R, Cica M, Richardoz M, Tomaszczyk M, Kramer A, Knapp S, Dunyach-Remy C, Rox K, Guichou JF, Lionne C, Hausch F Commun Chem. 2025 Dec 4;8(1):390. doi: 10.1038/s42004-025-01794-7. PMID:41345223<ref>PMID:41345223</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9qot" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Enterococcus casseliflavus]]
[[Category: Large Structures]]
[[Category: Gelin M]]
[[Category: Guichou JF]]
[[Category: Kowalewski J]]
[[Category: Lionne C]]
[[Category: Tomaszczyk M]]