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| | <StructureSection load='5tg6' size='340' side='right'caption='[[5tg6]], [[Resolution|resolution]] 1.78Å' scene=''> | | <StructureSection load='5tg6' size='340' side='right'caption='[[5tg6]], [[Resolution|resolution]] 1.78Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5tg6]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Aciba Aciba]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TG6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TG6 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5tg6]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Acinetobacter_baumannii Acinetobacter baumannii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TG6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5TG6 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BCT:BICARBONATE+ION'>BCT</scene>, <scene name='pdbligand=J4W:TERT-BUTYL+(1-HYDROXY-1,3-DIHYDRO-2,1-BENZOXABOROL-6-YL)CARBAMATE'>J4W</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.78Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ABA:ALPHA-AMINOBUTYRIC+ACID'>ABA</scene>, <scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ABA:ALPHA-AMINOBUTYRIC+ACID'>ABA</scene>, <scene name='pdbligand=BCT:BICARBONATE+ION'>BCT</scene>, <scene name='pdbligand=J4W:TERT-BUTYL+(1-HYDROXY-1,3-DIHYDRO-2,1-BENZOXABOROL-6-YL)CARBAMATE'>J4W</scene>, <scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5tg4|5tg4]], [[5tg5|5tg5]], [[5tg7|5tg7]]</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=5tg6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tg6 OCA], [https://pdbe.org/5tg6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5tg6 RCSB], [https://www.ebi.ac.uk/pdbsum/5tg6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5tg6 ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">blaOXA-33, bla-OXA-40, blaOXA-24, blaOXA-40, oxa-24, oxa40 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=470 ACIBA])</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=5tg6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tg6 OCA], [http://pdbe.org/5tg6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tg6 RCSB], [http://www.ebi.ac.uk/pdbsum/5tg6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tg6 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q8RLA6_ACIBA Q8RLA6_ACIBA] |
| | <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: Aciba]] | + | [[Category: Acinetobacter baumannii]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Mitchell, J M]] | + | [[Category: Mitchell JM]] |
| - | [[Category: Powers, R A]] | + | [[Category: Powers RA]] |
| - | [[Category: Werner, J P]] | + | [[Category: Werner JP]] |
| - | [[Category: Complex]]
| + | |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
| + | |
| - | [[Category: Inhibitor]]
| + | |
| - | [[Category: Lactamase]]
| + | |
| - | [[Category: Oxa]]
| + | |
| Structural highlights
5tg6 is a 1 chain structure with sequence from Acinetobacter baumannii. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 1.78Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
Q8RLA6_ACIBA
Publication Abstract from PubMed
beta-lactam antibiotics are crucial to the management of bacterial infections in the medical community. Due to overuse and misuse, clinically significant bacteria are now resistant to many commercially available antibiotics. The most widespread resistance mechanism to beta-lactams is the expression of beta-lactamase enzymes. To overcome beta-lactamase mediated resistance, inhibitors were designed to inactivate these enzymes. However, current inhibitors (clavulanic acid, tazobactam, and sulbactam) for beta-lactamases also contain the characteristic beta-lactam ring, making them susceptible to resistance mechanisms employed by bacteria. This presents a critical need for novel, non-beta-lactam inhibitors that can circumvent these resistance mechanisms. The carbapenem-hydrolyzing class D beta-lactamases (CHDLs) are of particular concern, given that they efficiently hydrolyze potent carbapenem antibiotics. Unfortunately, these enzymes are not inhibited by clinically available beta-lactamase inhibitors, nor are they effectively inhibited by the newest, non-beta-lactam inhibitor, avibactam. Boronic acids are known transition state analog inhibitors of class A and C beta-lactamases, and are not extensively characterized as inhibitors of class D beta-lactamases. Importantly, boronic acids provide a novel way to potentially inhibit class D beta-lactamases. Sixteen boronic acids were selected and tested for inhibition of the CHDL OXA-24/40. Several compounds were identified as effective inhibitors of OXA-24/40, with Ki values as low as 5 muM. The X-ray crystal structures of OXA-24/40 in complex with BA3, BA4, BA8, and BA16 were determined and revealed the importance of interactions with hydrophobic residues Tyr112 and Trp115. These boronic acids serve as progenitors in optimization efforts of a novel series of inhibitors for class D beta-lactamases. This article is protected by copyright. All rights reserved.
Exploring the potential of boronic acids as inhibitors of OXA-24/40 beta-lactamase.,Werner JP, Mitchell JM, Taracila MA, Bonomo RA, Powers RA Protein Sci. 2016 Dec 20. doi: 10.1002/pro.3100. PMID:27997706[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Werner JP, Mitchell JM, Taracila MA, Bonomo RA, Powers RA. Exploring the potential of boronic acids as inhibitors of OXA-24/40 beta-lactamase. Protein Sci. 2016 Dec 20. doi: 10.1002/pro.3100. PMID:27997706 doi:http://dx.doi.org/10.1002/pro.3100
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