9qp6: Difference between revisions
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==APH(2'')-IVa with an inhibitor== | |||
<StructureSection load='9qp6' size='340' side='right'caption='[[9qp6]], [[Resolution|resolution]] 2.35Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[9qp6]] 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=9QP6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9QP6 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]] 2.35Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1I80:(2~{S})-2-[4-(5-chloranyl-1~{H}-pyrrolo[2,3-b]pyridin-4-yl)-1,2,3-triazol-1-yl]propan-1-ol'>A1I80</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=9qp6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9qp6 OCA], [https://pdbe.org/9qp6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9qp6 RCSB], [https://www.ebi.ac.uk/pdbsum/9qp6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9qp6 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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 9qp6" style="background-color:#fffaf0;"></div> | ||
[[Category: Guichou | == References == | ||
[[Category: | <references/> | ||
[[Category: | __TOC__ | ||
[[Category: | </StructureSection> | ||
[[Category: Enterococcus casseliflavus]] | |||
[[Category: Large Structures]] | |||
[[Category: Gelin M]] | |||
[[Category: Guichou JF]] | |||
[[Category: Kowalewski J]] | |||
[[Category: Lionne C]] | |||
[[Category: Tomaszczyk M]] | |||
