View source for 7ato


==Structure of P. aeruginosa PBP3 in complex with an aryl boronic acid (Compound 2)==
<StructureSection load='7ato' size='340' side='right'caption='[[7ato]], [[Resolution|resolution]] 1.59&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7ATO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ATO 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]] 1.587&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=RXW:(5-methyl-1H-indazol-6-yl)boronic+acid'>RXW</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=7ato FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ato OCA], [https://pdbe.org/7ato PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ato RCSB], [https://www.ebi.ac.uk/pdbsum/7ato PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ato ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
The 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<ref>PMID:34337941</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7ato" style="background-color:#fffaf0;"></div>

==See Also==
*[[Penicillin-binding protein 3D structures|Penicillin-binding protein 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Bellini B]]
[[Category: Dowson CG]]
[[Category: Newman H]]