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5ll7
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==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]] | ||
Current revision
Crystal structure of KPC-2 carbapenemase in complex with a phenyl boronic inhibitor.
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