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| | <StructureSection load='4len' size='340' side='right'caption='[[4len]], [[Resolution|resolution]] 1.50Å' scene=''> | | <StructureSection load='4len' size='340' side='right'caption='[[4len]], [[Resolution|resolution]] 1.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4len]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LEN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4LEN FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4len]] is a 2 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=4LEN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LEN FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2GK:(2E)-3-[2-(DIHYDROXYBORANYL)-1-BENZOTHIOPHEN-3-YL]PROP-2-ENOIC+ACID'>2GK</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2GK:(2E)-3-[2-(DIHYDROXYBORANYL)-1-BENZOTHIOPHEN-3-YL]PROP-2-ENOIC+ACID'>2GK</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">blaCTX-M-9, blaCTX-M-9a, blaCTX-M-9a blaCTX-M-9 blaCTX-M-9b, blaCTX-M-9b ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</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=4len FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4len OCA], [https://pdbe.org/4len PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4len RCSB], [https://www.ebi.ac.uk/pdbsum/4len PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4len 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=4len FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4len OCA], [http://pdbe.org/4len PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4len RCSB], [http://www.ebi.ac.uk/pdbsum/4len PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4len ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q9L5C8_ECOLX Q9L5C8_ECOLX] |
| | <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 coli migula 1895]] | + | [[Category: Escherichia coli]] |
| - | [[Category: Beta-lactamase]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Tondi, D]] | + | [[Category: Tondi D]] |
| - | [[Category: Bacterial resistance]]
| + | |
| - | [[Category: Beta lactamase]]
| + | |
| - | [[Category: Binding site]]
| + | |
| - | [[Category: Boronic acid]]
| + | |
| - | [[Category: Broad spectrum]]
| + | |
| - | [[Category: Double perturbation cycle analysis]]
| + | |
| - | [[Category: Drug discovery]]
| + | |
| - | [[Category: Enzyme inhibitor]]
| + | |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
| + | |
| - | [[Category: Molecular]]
| + | |
| - | [[Category: Structure activity relationship]]
| + | |
| - | [[Category: Structure base drug design]]
| + | |
| - | [[Category: Thermodynamic]]
| + | |
| Structural highlights
Function
Q9L5C8_ECOLX
Publication Abstract from PubMed
Production of beta-lactamases (BLs) is the most widespread resistance mechanism adopted by bacteria to fight beta-lactam antibiotics. The substrate spectrum of BLs has become increasingly broad, posing a serious health problem. Thus, there is an urgent need for novel BL inhibitors. Boronic acid transition-state analogues are able to reverse the resistance conferred by class A and C BLs. We describe a boronic acid analogue possessing interesting and potent broad-spectrum activity vs class A and C serine-based BLs. Starting from benzo(b)thiophene-2-boronic acid (BZBTH2B), a nanomolar non-beta-lactam inhibitor of AmpC that can potentiate the activity of a third-generation cephalosporin against AmpC-producing resistant bacteria, we designed a novel broad-spectrum nanomolar inhibitor of class A and C BLs. Structure-based drug design (SBDD), synthesis, enzymology data, and X-ray crystallography results are discussed. We clarified the inhibitor binding geometry responsible for broad-spectrum activity vs serine-active BLs using double mutant thermodynamic cycle studies.
Targeting Class A and C Serine beta-Lactamases with a Broad-Spectrum Boronic Acid Derivative.,Tondi D, Venturelli A, Bonnet R, Pozzi C, Shoichet BK, Costi MP J Med Chem. 2014 Jun 16. PMID:24882105[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Tondi D, Venturelli A, Bonnet R, Pozzi C, Shoichet BK, Costi MP. Targeting Class A and C Serine beta-Lactamases with a Broad-Spectrum Boronic Acid Derivative. J Med Chem. 2014 Jun 16. PMID:24882105 doi:http://dx.doi.org/10.1021/jm5006572
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