9d7a
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==OXA-58-NA-1-157 5 min complex== | |
| + | <StructureSection load='9d7a' size='340' side='right'caption='[[9d7a]], [[Resolution|resolution]] 2.05Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[9d7a]] is a 4 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=9D7A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9D7A 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]] 2.05Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</scene>, <scene name='pdbligand=Y33:(5R)-5-[(1S,2R)-1-carboxy-2-hydroxypropyl]-3-{[(3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-yl]sulfanyl}-5-methyl-4,5-dihydro-1H-pyrrole-2-carboxylic+acid'>Y33</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=9d7a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9d7a OCA], [https://pdbe.org/9d7a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9d7a RCSB], [https://www.ebi.ac.uk/pdbsum/9d7a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9d7a ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/Q2TR58_ACIBA Q2TR58_ACIBA] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Antibiotic resistance in bacteria is a major global health concern. The wide spread of carbapenemases, bacterial enzymes that degrade the last-resort carbapenem antibiotics, is responsible for multidrug resistance in bacterial pathogens and has further significantly exacerbated this problem. Acinetobacter baumannii is one of the leading nosocomial pathogens due to the acquisition and wide dissemination of carbapenem-hydrolyzing class D beta-lactamases, which have dramatically diminished available therapeutic options. Thus, new antibiotics that are active against multidrug-resistantA. baumannii and carbapenemase inhibitors are urgently needed. Here we report characterization of the interaction of the C5alpha-methyl-substituted carbapenem NA-1-157 with one of the clinically important class D carbapenemases, OXA-58. Antibiotic susceptibility testing shows that the compound is more potent than commercial carbapenems against OXA-58-producingA. baumannii, with a clinically sensitive MIC value of 1 mug/mL. Kinetic studies demonstrate that NA-1-157 is a very poor substrate of the enzyme due mainly to a significantly reduced deacylation rate. Mass spectrometry analysis shows that inhibition of OXA-58 by NA-1-157 proceeds through both the classical acyl-enzyme intermediate and a reversible covalent species. Time-resolved X-ray crystallographic studies reveal that upon acylation of the enzyme, the compound causes progressive decarboxylation of the catalytic lysine residue, thus severely impairing deacylation. Overall, this study demonstrates that the carbapenem NA-1-157 is highly resistant to degradation by the OXA-58 carbapenemase. | ||
| - | + | Decarboxylation of the Catalytic Lysine Residue by the C5alpha-Methyl-Substituted Carbapenem NA-1-157 Leads to Potent Inhibition of the OXA-58 Carbapenemase.,Toth M, Stewart NK, Maggiolo AO, Quan P, Khan MMK, Buynak JD, Smith CA, Vakulenko SB ACS Infect Dis. 2024 Nov 27. doi: 10.1021/acsinfecdis.4c00671. PMID:39601221<ref>PMID:39601221</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 9d7a" style="background-color:#fffaf0;"></div> |
| - | [[Category: Smith | + | == References == |
| - | [[Category: | + | <references/> |
| - | [[Category: Vakulenko | + | __TOC__ |
| + | </StructureSection> | ||
| + | [[Category: Acinetobacter baumannii]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Maggiolo AO]] | ||
| + | [[Category: Smith CA]] | ||
| + | [[Category: Toth M]] | ||
| + | [[Category: Vakulenko SB]] | ||
Revision as of 20:08, 11 December 2024
OXA-58-NA-1-157 5 min complex
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