5ll7: Difference between revisions
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==Crystal structure of KPC-2 carbapenemase in complex with a phenyl boronic inhibitor.== | |||
<StructureSection load='5ll7' size='340' side='right'caption='[[5ll7]], [[Resolution|resolution]] 1.40Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5ll7]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LL7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5LL7 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]] 1.4Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6YV:(~{E})-3-[2-(dihydroxyboranyl)phenyl]prop-2-enoic+acid'>6YV</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=5ll7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ll7 OCA], [https://pdbe.org/5ll7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ll7 RCSB], [https://www.ebi.ac.uk/pdbsum/5ll7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ll7 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/A0A0H4IUK8_ECOLX A0A0H4IUK8_ECOLX] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The emergence and dissemination of multidrug resistant (MDR) pathogens resistant to nearly all available antibiotics poses a significant threat in clinical therapy. Among them, Klebsiella pneumoniae clinical isolates overexpressing KPC-2 carbapenemase are the most worrisome, extending bacterial resistance to last-resort carbapenems. In this study, we investigate the molecular recognition requirements in the KPC-2 active site by small phenylboronic acid derivatives. Four new phenylboronic acid derivatives were designed and tested against KPC-2. For the most active, despite their simple chemical structures, nanomolar affinity was achieved. The new derivatives restored susceptibility to meropenem in clinical strains overexpressing KPC-2. Moreover, no cytotoxicity was detected in cell-viability assays, which further validated the designed leads. Two crystallographic binary complexes of the best inhibitors binding KPC-2 were obtained at high resolution. Kinetic descriptions of slow binding, time-dependent inhibition, and interaction geometries in KPC-2 were fully investigated. This study will ultimately lead toward the optimization and development of more-effective KPC-2 inhibitors. | |||
Phenylboronic Acid Derivatives as Validated Leads Active in Clinical Strains Overexpressing KPC-2: A Step against Bacterial Resistance.,Celenza G, Vicario M, Bellio P, Linciano P, Perilli M, Oliver A, Blazquez J, Cendron L, Tondi D ChemMedChem. 2018 Apr 6;13(7):713-724. doi: 10.1002/cmdc.201700788. Epub 2018 Feb, 20. PMID:29356380<ref>PMID:29356380</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[ | </div> | ||
[[Category: | <div class="pdbe-citations 5ll7" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: Bellio | ==See Also== | ||
[[Category: Celenza | *[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] | ||
[[Category: Perilli | == References == | ||
[[Category: Vicario | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Escherichia coli]] | |||
[[Category: Large Structures]] | |||
[[Category: Bellio P]] | |||
[[Category: Celenza G]] | |||
[[Category: Cendron L]] | |||
[[Category: Perilli MG]] | |||
[[Category: Tondi D]] | |||
[[Category: Vicario M]] | |||
Latest revision as of 18:32, 18 October 2023
Crystal structure of KPC-2 carbapenemase in complex with a phenyl boronic inhibitor.
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