7au0: Difference between revisions
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<StructureSection load='7au0' size='340' side='right'caption='[[7au0]], [[Resolution|resolution]] 2.17Å' scene=''> | <StructureSection load='7au0' size='340' side='right'caption='[[7au0]], [[Resolution|resolution]] 2.17Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'> | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AU0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AU0 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]] 2.17Å</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]] 2.17Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=S0Z:methyl+(R)-2-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborole-6-carboxamido)-2-phenylacetate'>S0Z</scene></td></tr> | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=S0Z:methyl+(R)-2-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborole-6-carboxamido)-2-phenylacetate'>S0Z</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=7au0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7au0 OCA], [https://pdbe.org/7au0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7au0 RCSB], [https://www.ebi.ac.uk/pdbsum/7au0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7au0 ProSAT]</span></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=7au0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7au0 OCA], [https://pdbe.org/7au0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7au0 RCSB], [https://www.ebi.ac.uk/pdbsum/7au0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7au0 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Bellini B]] | [[Category: Bellini B]] | ||
[[Category: Dowson CG]] | [[Category: Dowson CG]] | ||
[[Category: Newman H]] | [[Category: Newman H]] | ||
Latest revision as of 11:34, 17 October 2024
Structure of P. aeruginosa PBP3 in complex with a benzoxaborole (Compound 7)Structure of P. aeruginosa PBP3 in complex with a benzoxaborole (Compound 7)
Structural highlights
Publication Abstract from PubMedThe effectiveness of beta-lactam antibiotics is increasingly compromised by beta-lactamases. Boron-containing inhibitors are potent serine-beta-lactamase inhibitors, but the interactions of boron-based compounds with the penicillin-binding protein (PBP) beta-lactam targets have not been extensively studied. We used high-throughput X-ray crystallography to explore reactions of a boron-containing fragment set with the Pseudomonas aeruginosa PBP3 (PaPBP3). Multiple crystal structures reveal that boronic acids react with PBPs to give tricovalently linked complexes bonded to Ser294, Ser349, and Lys484 of PaPBP3; benzoxaboroles react with PaPBP3 via reaction with two nucleophilic serines (Ser294 and Ser349) to give dicovalently linked complexes; and vaborbactam reacts to give a monocovalently linked complex. Modifications of the benzoxaborole scaffold resulted in a moderately potent inhibition of PaPBP3, though no antibacterial activity was observed. Overall, the results further evidence the potential for the development of new classes of boron-based antibiotics, which are not compromised by beta-lactamase-driven resistance. High-Throughput Crystallography Reveals Boron-Containing Inhibitors of a Penicillin-Binding Protein with Di- and Tricovalent Binding Modes.,Newman H, Krajnc A, Bellini D, Eyermann CJ, Boyle GA, Paterson NG, McAuley KE, Lesniak R, Gangar M, von Delft F, Brem J, Chibale K, Schofield CJ, Dowson CG J Med Chem. 2021 Jul 31. doi: 10.1021/acs.jmedchem.1c00717. PMID:34337941[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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