View source for 7aux


==Crystal structure of OXA-48 beta-lactamase in the complex with the inhbitor ID2==
<StructureSection load='7aux' size='340' side='right'caption='[[7aux]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7aux]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Klebsiella_pneumoniae Klebsiella pneumoniae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AUX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AUX 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]] 2.05&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</scene>, <scene name='pdbligand=LKW:6-(4-carboxyphenyl)-3-(4-ethylphenyl)-2~{H}-pyrazolo[3,4-b]pyridine-4-carboxylic+acid'>LKW</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=7aux FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7aux OCA], [https://pdbe.org/7aux PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7aux RCSB], [https://www.ebi.ac.uk/pdbsum/7aux PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7aux ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q6XEC0_KLEPN Q6XEC0_KLEPN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The major cause of bacterial resistance to beta-lactams is the production of hydrolytic beta-lactamase enzymes. Nowadays, the combination of beta-lactam antibiotics with beta-lactamase inhibitors (BLIs) is the main strategy for overcoming such issues. Nevertheless, particularly challenging beta-lactamases, such as OXA-48, pose the need for novel and effective treatments. Herein, we describe the screening of a proprietary compound collection against Klebsiella pneumoniae OXA-48, leading to the identification of several chemotypes, like the 4-ideneamino-4H-1,2,4-triazole (SC_2) and pyrazolo[3,4-b]pyridine (SC_7) cores as potential inhibitors. Importantly, the most potent representative of the latter series (ID2, AC50 = 0.99 muM) inhibited OXA-48 via a reversible and competitive mechanism of action, as demonstrated by biochemical and X-ray studies; furthermore, it slightly improved imipenem's activity in Escherichia coli ATCC BAA-2523 beta-lactam resistant strain. Also, ID2 showed good solubility and no sign of toxicity up to the highest tested concentration, resulting in a promising starting point for further optimization programs toward novel and effective non-beta-lactam BLIs.

Discovery of Novel Chemical Series of OXA-48 beta-Lactamase Inhibitors by High-Throughput Screening.,Garofalo B, Prati F, Buonfiglio R, Coletta I, D'Atanasio N, Molteni A, Carettoni D, Wanke V, Pochetti G, Montanari R, Capelli D, Milanese C, Di Giorgio FP, Ombrato R Pharmaceuticals (Basel). 2021 Jun 25;14(7). pii: ph14070612. doi:, 10.3390/ph14070612. PMID:34202402<ref>PMID:34202402</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7aux" style="background-color:#fffaf0;"></div>

==See Also==
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Klebsiella pneumoniae]]
[[Category: Large Structures]]
[[Category: Capelli D]]
[[Category: Garofalo B]]
[[Category: Montanari R]]
[[Category: Ombrato R]]
[[Category: Pochetti G]]