View source for 5mgi


==Crystal structure of KPC-2 carbapenemase in complex with a phenyl boronic inhibitor.==
<StructureSection load='5mgi' size='340' side='right'caption='[[5mgi]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5mgi]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Klebsiella_oxytoca Klebsiella oxytoca]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MGI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MGI 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]] 1.5&#8491;</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></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=5mgi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mgi OCA], [https://pdbe.org/5mgi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mgi RCSB], [https://www.ebi.ac.uk/pdbsum/5mgi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mgi ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/BLKPC_KLEOX BLKPC_KLEOX] 
<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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5mgi" style="background-color:#fffaf0;"></div>

==See Also==
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Klebsiella oxytoca]]
[[Category: Large Structures]]
[[Category: Bellio P]]
[[Category: Celenza G]]
[[Category: Cendron L]]
[[Category: Perilli MG]]
[[Category: Tondi D]]
[[Category: Vicario M]]