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7lc4
From Proteopedia
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<StructureSection load='7lc4' size='340' side='right'caption='[[7lc4]], [[Resolution|resolution]] 2.00Å' scene=''> | <StructureSection load='7lc4' size='340' side='right'caption='[[7lc4]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'> | + | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LC4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LC4 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=XVG:1-[(2S)-2-{[(2Z)-2-(2-amino-5-chloro-1,3-thiazol-4-yl)-2-{[(2-carboxypropan-2-yl)oxy]imino}acetyl]amino}-3-oxopropyl]-4-{[2-(5,6-dihydroxy-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]carbamoyl}-2,5-dihydro-1H-pyrazole-3-carboxylic+acid'>XVG</scene | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> |
| - | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=XVG:1-[(2S)-2-{[(2Z)-2-(2-amino-5-chloro-1,3-thiazol-4-yl)-2-{[(2-carboxypropan-2-yl)oxy]imino}acetyl]amino}-3-oxopropyl]-4-{[2-(5,6-dihydroxy-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]carbamoyl}-2,5-dihydro-1H-pyrazole-3-carboxylic+acid'>XVG</scene></td></tr> | |
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7lc4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lc4 OCA], [https://pdbe.org/7lc4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lc4 RCSB], [https://www.ebi.ac.uk/pdbsum/7lc4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lc4 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=7lc4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lc4 OCA], [https://pdbe.org/7lc4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lc4 RCSB], [https://www.ebi.ac.uk/pdbsum/7lc4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lc4 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | Serious infections caused by multidrug-resistant (MDR) organisms (Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii) present a critical need for innovative drug development. Herein, we describe the preclinical evaluation of YU253911, 2, a novel gamma-lactam siderophore antibiotic with potent antimicrobial activity against MDR Gram-negative pathogens. Penicillin-binding protein (PBP) 3 was shown to be a target of 2 using a binding assay with purified P. aeruginosa PBP3. The specific binding interactions with P. aeruginosa were further characterized with a high-resolution (2.0 A) X-ray structure of the compound's acylation product in P. aeruginosa PBP3. Compound 2 was shown to have a concentration >1 mug/ml at the 6 h time point when administered intravenously or subcutaneously in mice. Employing a meropenem resistant strain of P. aeruginosa, 2 was shown to have dose-dependent efficacy at 50 and 100 mg/kg q6h dosing in a mouse thigh infection model. Lastly, we showed that a novel gamma-lactam and beta-lactamase inhibitor (BLI) combination can effectively lower minimum inhibitory concentrations (MICs) against carbapenem resistant Acinetobacter spp. that demonstrated decreased susceptibility to 2 alone. | ||
| - | + | ==See Also== | |
| - | + | *[[Penicillin-binding protein 3D structures|Penicillin-binding protein 3D structures]] | |
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Kumar V]] |
| - | [[Category: Akker | + | [[Category: Van den Akker F]] |
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Current revision
Crystal structure of Pseudomonas aeruginosa PBP3 in complex with gamma-lactam YU253911
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