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| | <StructureSection load='5mgi' size='340' side='right'caption='[[5mgi]], [[Resolution|resolution]] 1.50Å' scene=''> | | <StructureSection load='5mgi' size='340' side='right'caption='[[5mgi]], [[Resolution|resolution]] 1.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5mgi]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_oxytocus_perniciosus"_flugge_1886 "bacillus oxytocus perniciosus" flugge 1886]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MGI FirstGlance]. <br> | + | <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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6YV:(~{E})-3-[2-(dihydroxyboranyl)phenyl]prop-2-enoic+acid'>6YV</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.5Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5ll7|5ll7]]</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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">bla, kpc, kpc2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=571 "Bacillus oxytocus perniciosus" Flugge 1886])</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> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.6 3.5.2.6] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5mgi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mgi OCA], [http://pdbe.org/5mgi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mgi RCSB], [http://www.ebi.ac.uk/pdbsum/5mgi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mgi ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/BLKPC_KLEOX BLKPC_KLEOX] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bacillus oxytocus perniciosus flugge 1886]] | + | [[Category: Klebsiella oxytoca]] |
| - | [[Category: Beta-lactamase]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Bellio, P]] | + | [[Category: Bellio P]] |
| - | [[Category: Celenza, G]] | + | [[Category: Celenza G]] |
| - | [[Category: Cendron, L]] | + | [[Category: Cendron L]] |
| - | [[Category: Perilli, M G]] | + | [[Category: Perilli MG]] |
| - | [[Category: Tondi, D]] | + | [[Category: Tondi D]] |
| - | [[Category: Vicario, M]] | + | [[Category: Vicario M]] |
| - | [[Category: Carbapenemase]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Phenyl boronic inhibitor]]
| + | |
| Structural highlights
Function
BLKPC_KLEOX
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Celenza G, Vicario M, Bellio P, Linciano P, Perilli M, Oliver A, Blazquez J, Cendron L, Tondi D. Phenylboronic Acid Derivatives as Validated Leads Active in Clinical Strains Overexpressing KPC-2: A Step against Bacterial Resistance. ChemMedChem. 2018 Apr 6;13(7):713-724. doi: 10.1002/cmdc.201700788. Epub 2018 Feb, 20. PMID:29356380 doi:http://dx.doi.org/10.1002/cmdc.201700788
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