7auh: Difference between revisions
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==Structure of P. aeruginosa PBP3 in complex with vaborbactam== | ==Structure of P. aeruginosa PBP3 in complex with vaborbactam== | ||
<StructureSection load='7auh' size='340' side='right'caption='[[7auh]]' scene=''> | <StructureSection load='7auh' size='340' side='right'caption='[[7auh]], [[Resolution|resolution]] 2.01Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AUH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AUH FirstGlance]. <br> | <table><tr><td colspan='2'>[[7auh]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseae Pseae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AUH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AUH FirstGlance]. <br> | ||
</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=7auh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7auh OCA], [https://pdbe.org/7auh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7auh RCSB], [https://www.ebi.ac.uk/pdbsum/7auh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7auh ProSAT]</span></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4D6:{(3R,6S)-2-HYDROXY-3-[(THIOPHEN-2-YLACETYL)AMINO]-1,2-OXABORINAN-6-YL}ACETIC+ACID'>4D6</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[7atm|7atm]], [[7ato|7ato]], [[7atw|7atw]], [[7atx|7atx]], [[7au0|7au0]], [[7au1|7au1]], [[7au8|7au8]], [[7au9|7au9]], [[7aub|7aub]]</div></td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ftsI, pbpB, PA4418 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=208964 PSEAE])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Serine-type_D-Ala-D-Ala_carboxypeptidase Serine-type D-Ala-D-Ala carboxypeptidase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.16.4 3.4.16.4] </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=7auh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7auh OCA], [https://pdbe.org/7auh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7auh RCSB], [https://www.ebi.ac.uk/pdbsum/7auh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7auh ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[[https://www.uniprot.org/uniprot/FTSI_PSEAE FTSI_PSEAE]] Catalyzes cross-linking of the peptidoglycan cell wall at the division septum (By similarity). Binds penicillin (PubMed:20580675).[HAMAP-Rule:MF_02080]<ref>PMID:20580675</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== 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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7auh" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Bellini B]] | [[Category: Pseae]] | ||
[[Category: Dowson | [[Category: Serine-type D-Ala-D-Ala carboxypeptidase]] | ||
[[Category: Newman H]] | [[Category: Bellini, B]] | ||
[[Category: Dowson, C G]] | |||
[[Category: Newman, H]] | |||
[[Category: Boron-binding]] | |||
[[Category: D-transpeptidase]] | |||
[[Category: Hydrolase]] | |||
Revision as of 09:58, 22 September 2021
Structure of P. aeruginosa PBP3 in complex with vaborbactamStructure of P. aeruginosa PBP3 in complex with vaborbactam
Structural highlights
Function[FTSI_PSEAE] Catalyzes cross-linking of the peptidoglycan cell wall at the division septum (By similarity). Binds penicillin (PubMed:20580675).[HAMAP-Rule:MF_02080][1] 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[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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