6t5y

<table><tr><td colspan='2'>[[6t5y]] 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=6T5Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6T5Y FirstGlance]. <br>

== Function ==

[https://www.uniprot.org/uniprot/AMPC_ECOLI AMPC_ECOLI] This protein is a serine beta-lactamase with a substrate specificity for cephalosporins.

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== 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>

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== References ==

<references/>

[[Category: Escherichia coli K-12]]