6tpm: Difference between revisions
From Proteopedia
Jump to navigationJump to search
m Protected "6tpm" [edit=sysop:move=sysop] |
No edit summary |
||
| (2 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
The | ==Crystal structure of AmpC from E.coli with Relebactam (MK-7655)== | ||
<StructureSection load='6tpm' size='340' side='right'caption='[[6tpm]], [[Resolution|resolution]] 1.72Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6tpm]] 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=6TPM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TPM 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]] 1.72Å</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=MK7:(2S,5R)-1-FORMYL-N-(PIPERIDIN-4-YL)-5-[(SULFOOXY)AMINO]PIPERIDINE-2-CARBOXAMIDE'>MK7</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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=6tpm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tpm OCA], [https://pdbe.org/6tpm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6tpm RCSB], [https://www.ebi.ac.uk/pdbsum/6tpm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6tpm ProSAT]</span></td></tr> | |||
</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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6tpm" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Escherichia coli K-12]] | |||
[[Category: Large Structures]] | |||
[[Category: Brem J]] | |||
[[Category: Lang PA]] | |||
[[Category: Leissing TM]] | |||
[[Category: Schofield CJ]] | |||
