4hef: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4hef]] 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=4HEF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HEF FirstGlance]. <br> | <table><tr><td colspan='2'>[[4hef]] 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=4HEF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HEF FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NXL:(2S,5R)-1-FORMYL-5-[(SULFOOXY)AMINO]PIPERIDINE-2-CARBOXAMIDE'>NXL</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]] 1.86Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NXL:(2S,5R)-1-FORMYL-5-[(SULFOOXY)AMINO]PIPERIDINE-2-CARBOXAMIDE'>NXL</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=4hef FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hef OCA], [https://pdbe.org/4hef PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hef RCSB], [https://www.ebi.ac.uk/pdbsum/4hef PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hef 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=4hef FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hef OCA], [https://pdbe.org/4hef PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hef RCSB], [https://www.ebi.ac.uk/pdbsum/4hef PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hef ProSAT]</span></td></tr> | ||
</table> | </table> | ||
Latest revision as of 13:04, 30 October 2024
Structure of avibactam bound to Pseudomonas aeruginosa AmpCStructure of avibactam bound to Pseudomonas aeruginosa AmpC
Structural highlights
FunctionPublication Abstract from PubMedAlthough beta-lactams have been the most effective class of antibacterial agents used in clinical practice for the past half century, their effectiveness on Gram-negative bacteria has been eroded due to the emergence and spread of beta-lactamase enzymes that are not affected by currently marketed beta-lactam/beta-lactamase inhibitor combinations. Avibactam is a novel, covalent, non-beta-lactam beta-lactamase inhibitor presently in clinical development in combination with either ceftaroline or ceftazidime. In vitro studies show that avibactam may restore the broad-spectrum activity of cephalosporins against class A, class C and some class D beta-lactamases. Here we describe the structure of two clinically important beta-lactamase enzymes bound to avibactam, the class A CTX-M-15 extended-spectrum beta-lactamase and class C Pseudomonas aeruginosa AmpC beta-lactamase, which together provide insight into the binding modes for the respective enzyme classes. The structure reveals a similar binding mode in both enzymes and thus provides a rationale for the broad-spectrum inhibitory activity of avibactam. Identification of the key residues surrounding the binding pocket allows for a better understanding of the potency of this scaffold. Finally, avibactam has recently been shown to be a reversible inhibitor and the structure provides insights into the mechanism of avibactam recyclization. Analysis of the ultra-high resolution CTX-M-15 structure suggests how the deacylation mechanism favors recyclization over hydrolysis. Structural Insight into Potent Broad-spectrum Inhibition with Reversible Recyclization Mechanism: Avibactam in Complex with CTX-M-15 and Pseudomonas aeruginosa AmpC beta-lactamases.,Lahiri SD, Mangani S, Durand-Reville T, Benvenuti M, De Luca F, Sanyal G, Docquier JD Antimicrob Agents Chemother. 2013 Feb 25. PMID:23439634[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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