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<StructureSection load='7lc4' size='340' side='right'caption='[[7lc4]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
<StructureSection load='7lc4' size='340' side='right'caption='[[7lc4]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[7lc4]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa]. 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>
<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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</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]] 2&#8491;</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='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='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>
== 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 ==
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 &gt;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.
A gamma-lactam siderophore antibiotic effective against multidrug-resistant Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter spp.,Goldberg JA, Kumar V, Spencer EJ, Hoyer D, Marshall SH, Hujer AM, Hujer KM, Bethel CR, Papp-Wallace KM, Perez F, Jacobs MR, van Duin D, Kreiswirth BN, van den Akker F, Plummer MS, Bonomo RA Eur J Med Chem. 2021 Apr 8;220:113436. doi: 10.1016/j.ejmech.2021.113436. PMID:33933754<ref>PMID:33933754</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7lc4" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Penicillin-binding protein 3D structures|Penicillin-binding protein 3D structures]]
*[[Penicillin-binding protein 3D structures|Penicillin-binding protein 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Pseudomonas aeruginosa]]
[[Category: Kumar V]]
[[Category: Kumar V]]
[[Category: Van den Akker F]]
[[Category: Van den Akker F]]

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