7r6z: Difference between revisions
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New page: '''Unreleased structure''' The entry 7r6z is ON HOLD Authors: Taylor, D.M., Hu, L., Prasad, B.V.V., Sankaran, B., Palzkill, T. Description: OXA-48 bound by Compound 3.3 [[Category: Unr... |
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==OXA-48 bound by Compound 3.3== | |||
<StructureSection load='7r6z' size='340' side='right'caption='[[7r6z]], [[Resolution|resolution]] 2.10Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7r6z]] 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=7R6Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7R6Z 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]] 2.1Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3I0:4-amino-5-hydroxynaphthalene-2,7-disulfonic+acid'>3I0</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</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=7r6z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7r6z OCA], [https://pdbe.org/7r6z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7r6z RCSB], [https://www.ebi.ac.uk/pdbsum/7r6z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7r6z ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q6XEC0_KLEPN Q6XEC0_KLEPN] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Despite the advances in beta-lactamase inhibitor development, limited options exist for the class D carbapenemase known as OXA-48. OXA-48 is one of the most prevalent carbapenemases in carbapenem-resistant Enterobacteriaceae infections and is not susceptible to most available beta-lactamase inhibitors. Here, we screened various low-molecular-weight compounds (fragments) against OXA-48 to identify functional scaffolds for inhibitor development. Several biphenyl-, naphthalene-, fluorene-, anthraquinone-, and azobenzene-based compounds were found to inhibit OXA-48 with low micromolar potency despite their small size. Co-crystal structures of OXA-48 with several of these compounds revealed key interactions with the carboxylate-binding pocket, Arg214, and various hydrophobic residues of beta-lactamase that can be exploited in future inhibitor development. A number of the low-micromolar-potency inhibitors, across different scaffolds, synergize with ampicillin to kill Escherichia coli expressing OXA-48, albeit at high concentrations of the respective inhibitors. Additionally, several compounds demonstrated micromolar potency toward the OXA-24 and OXA-58 class D carbapenemases that are prevalent in Acinetobacter baumannii. This work provides foundational information on a variety of chemical scaffolds that can guide the design of effective OXA-48 inhibitors that maintain efficacy as well as potency toward other major class D carbapenemases. | |||
Unique Diacidic Fragments Inhibit the OXA-48 Carbapenemase and Enhance the Killing of Escherichia coli Producing OXA-48.,Taylor DM, Anglin J, Hu L, Wang L, Sankaran B, Wang J, Matzuk MM, Prasad BVV, Palzkill T ACS Infect Dis. 2021 Nov 24. doi: 10.1021/acsinfecdis.1c00501. PMID:34817169<ref>PMID:34817169</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Hu | <div class="pdbe-citations 7r6z" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: Prasad | ==See Also== | ||
[[Category: | *[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] | ||
[[Category: | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Klebsiella pneumoniae]] | |||
[[Category: Large Structures]] | |||
[[Category: Hu L]] | |||
[[Category: Palzkill T]] | |||
[[Category: Prasad BVV]] | |||
[[Category: Sankaran B]] | |||
[[Category: Taylor DM]] | |||
