|
|
| Line 3: |
Line 3: |
| | <StructureSection load='7aub' size='340' side='right'caption='[[7aub]], [[Resolution|resolution]] 1.91Å' scene=''> | | <StructureSection load='7aub' size='340' side='right'caption='[[7aub]], [[Resolution|resolution]] 1.91Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[7aub]] 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=7AUB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AUB FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7aub]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa_PAO1 Pseudomonas aeruginosa PAO1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AUB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AUB FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=S1K:2-(5-(benzyloxy)-1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-3-yl)acetic+acid'>S1K</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]] 1.907Å</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]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=S1K:2-(5-(benzyloxy)-1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-3-yl)acetic+acid'>S1K</scene></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=7aub FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7aub OCA], [https://pdbe.org/7aub PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7aub RCSB], [https://www.ebi.ac.uk/pdbsum/7aub PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7aub 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=7aub FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7aub OCA], [https://pdbe.org/7aub PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7aub RCSB], [https://www.ebi.ac.uk/pdbsum/7aub PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7aub ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == 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>
| + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 21: |
Line 19: |
| | </div> | | </div> |
| | <div class="pdbe-citations 7aub" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 7aub" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Penicillin-binding protein 3D structures|Penicillin-binding protein 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| Line 26: |
Line 27: |
| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Pseae]] | + | [[Category: Pseudomonas aeruginosa PAO1]] |
| - | [[Category: Serine-type D-Ala-D-Ala carboxypeptidase]]
| + | [[Category: Bellini B]] |
| - | [[Category: Bellini, B]] | + | [[Category: Dowson CG]] |
| - | [[Category: Dowson, C G]] | + | [[Category: Newman H]] |
| - | [[Category: Newman, H]] | + | |
| - | [[Category: Boron-binding]]
| + | |
| - | [[Category: D-transpeptidase]]
| + | |
| - | [[Category: Divalency]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| 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 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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ de Leon SR, Daniels K, Clarke AJ. Production and purification of the penicillin-binding protein 3 from Pseudomonas aeruginosa. Protein Expr Purif. 2010 Oct;73(2):177-83. doi: 10.1016/j.pep.2010.05.005. Epub, 2010 May 16. PMID:20580675 doi:http://dx.doi.org/10.1016/j.pep.2010.05.005
- ↑ 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. High-Throughput Crystallography Reveals Boron-Containing Inhibitors of a Penicillin-Binding Protein with Di- and Tricovalent Binding Modes. J Med Chem. 2021 Jul 31. doi: 10.1021/acs.jmedchem.1c00717. PMID:34337941 doi:http://dx.doi.org/10.1021/acs.jmedchem.1c00717
|
