View source for 9qpl


==APH(2'')-IVa with an inhibitor==
<StructureSection load='9qpl' size='340' side='right'caption='[[9qpl]], [[Resolution|resolution]] 2.04&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9qpl]] 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=9QPL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9QPL 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]] 2.04&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1I86:5-chloranyl-2-(cyclopropylamino)-~{N}-[2-(1-phenylpyrazol-3-yl)ethyl]pyridine-4-carboxamide'>A1I86</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=9qpl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9qpl OCA], [https://pdbe.org/9qpl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9qpl RCSB], [https://www.ebi.ac.uk/pdbsum/9qpl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9qpl ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/O68183_ENTCA O68183_ENTCA] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
According to the World Health Organization (WHO), antimicrobial resistance is a serious global health issue. Overcoming antibiotic resistance involves several strategies, including the inhibition of resistance mechanisms. Among the various resistance mechanisms, aminoglycoside phosphotransferases (APHs) catalyze the transfer of the gamma-phosphate from a nucleotide donor to various aminoglycosides, leading to their inactivation. In this work, using a fragment-based drug design (FBDD) approach, we have identified and characterized a promising APH inhibitor capable of increasing the sensitivity of Pseudomonas aeruginosa and Staphylococcus aureus resistant to aminoglycosides. It is therefore a good candidate for the future development of APH inhibitors to be prescribed in combination with aminoglycosides. This molecule is a competitive inhibitor of adenosine 5'-triphosphate (ATP), the phosphate donor of APHs. Further studies are required to optimize this molecule to improve its specificity for APHs and its bioavailability in bacteria.

Fragment-based drug design of a bacterial kinase inhibitor capable of increasing the antibiotic sensitivity of clinical isolates.,Kowalewski J, Deutscher R, Richardoz M, Tomaszczyk M, Gelin M, Labesse G, Hausch F, Wright GD, Dunyach-Remy C, Guichou JF, Lionne C Commun Chem. 2025 Nov 27;8(1):417. doi: 10.1038/s42004-025-01795-6. PMID:41310159<ref>PMID:41310159</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9qpl" 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]]