6t7l: Difference between revisions

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<StructureSection load='6t7l' size='340' side='right'caption='[[6t7l]], [[Resolution|resolution]] 1.47&Aring;' scene=''>
<StructureSection load='6t7l' size='340' side='right'caption='[[6t7l]], [[Resolution|resolution]] 1.47&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6t7l]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6T7L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6T7L FirstGlance]. <br>
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6T7L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6T7L 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]] 1.47&#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]] 1.47&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=OP0:(2S,5R)-N-(2-AMINOETHOXY)-1-FORMYL-5-[(SULFOOXY)AMINO]PIPERIDINE-2-CARBOXAMIDE'>OP0</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=OP0:(2S,5R)-N-(2-AMINOETHOXY)-1-FORMYL-5-[(SULFOOXY)AMINO]PIPERIDINE-2-CARBOXAMIDE'>OP0</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=6t7l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6t7l OCA], [https://pdbe.org/6t7l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6t7l RCSB], [https://www.ebi.ac.uk/pdbsum/6t7l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6t7l 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=6t7l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6t7l OCA], [https://pdbe.org/6t7l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6t7l RCSB], [https://www.ebi.ac.uk/pdbsum/6t7l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6t7l ProSAT]</span></td></tr>
</table>
</table>
== Function ==
[https://www.uniprot.org/uniprot/AMPC_ECOLI AMPC_ECOLI] This protein is a serine beta-lactamase with a substrate specificity for cephalosporins.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
beta-Lactam antibiotics are presently the most important treatments for infections by pathogenic Escherichia coli, but their use is increasingly compromised by beta-lactamases, including the chromosomally encoded class C AmpC serine-beta-lactamases (SBLs). The diazabicyclooctane (DBO) avibactam is a potent AmpC inhibitor; the clinical success of avibactam combined with ceftazidime has stimulated efforts to optimize the DBO core. We report kinetic and structural studies, including four high-resolution crystal structures, concerning inhibition of the AmpC serine-beta-lactamase from E. coli (AmpC (EC) ) by clinically relevant DBO-based inhibitors: avibactam, relebactam, nacubactam, and zidebactam. Kinetic analyses and mass spectrometry-based assays were used to study their mechanisms of AmpC (EC) inhibition. The results reveal that, under our assay conditions, zidebactam manifests increased potency (apparent inhibition constant [K(iapp)], 0.69 muM) against AmpC (EC) compared to that of the other DBOs (K(iapp) = 5.0 to 7.4 muM) due to an approximately 10-fold accelerated carbamoylation rate. However, zidebactam also has an accelerated off-rate, and with sufficient preincubation time, all the DBOs manifest similar potencies. Crystallographic analyses indicate a greater conformational freedom of the AmpC (EC) -zidebactam carbamoyl complex compared to those for the other DBOs. The results suggest the carbamoyl complex lifetime should be a consideration in development of DBO-based SBL inhibitors for the clinically important class C SBLs.
Structural Investigations of the Inhibition of Escherichia coli AmpC beta-Lactamase by Diazabicyclooctanes.,Lang PA, Leissing TM, Page MGP, Schofield CJ, Brem J Antimicrob Agents Chemother. 2021 Jan 20;65(2):e02073-20. doi: , 10.1128/AAC.02073-20. Print 2021 Jan 20. PMID:33199391<ref>PMID:33199391</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6t7l" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Escherichia coli K-12]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Brem J]]
[[Category: Brem J]]

Latest revision as of 08:48, 21 November 2024

Crystal structure of AmpC from E.coli with Nacubactam (OP0595)Crystal structure of AmpC from E.coli with Nacubactam (OP0595)

Structural highlights

Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.47Å
Ligands:, , , , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

See Also

6t7l, resolution 1.47Å

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OCA
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