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@ARTICLE{Gore:642342,
author = {Gore, Gargi and Prester, Andreas and von Stetten, David and
Bartels, Kim and Schulz, Eike C.},
title = {{B}inding mode of {I}soxazolyl {P}enicillins to a
{C}lass-{A} β-lactamase at ambient conditions},
journal = {Communications chemistry},
volume = {8},
number = {1},
issn = {2399-3669},
address = {[London]},
publisher = {Macmillan Publishers Limited, part of Springer Nature},
reportid = {PUBDB-2025-05497},
pages = {387},
year = {2025},
abstract = {The predominant resistance mechanism observed in
Gram-negative bacteria involves the production of
β-lactamases, which catalyse the hydrolysis of β-lactam
antibiotics, thereby rendering them ineffective. Although
Isoxazolyl Penicillins have been available since the 1970s,
there are currently no structures in complex with class-A
β-lactamases available. Here we have analysed the structure
of the clinically relevant β-lactamase CTX-M-14 from
Klebsiella pneumoniae near physiological temperatures, via
serial synchrotron crystallography. We demonstrate the
acyl-enzyme intermediates of the catalytically impaired
CTX-M-14 mutant E166A in complex with three
Isoxazolyl-Penicillins: Oxacillin, Cloxacillin and
Dicloxacillin. Structural comparisons of CTX-M-Penicillin
complexes show that, while conserved active-site
interactions are maintained, each Isoxazolyl-Penicillin
adopts a distinct conformation. While the three derivatives
differ only by one and two chlorine atoms, respectively,
their conformational heterogeneity appears to be increased
by chlorination of the phenyl ring.},
cin = {MPSD},
ddc = {540},
cid = {I:(DE-H253)MPSD-20120731},
pnm = {DFG project G:(GEPRIS)458246365 - Zeitaufgelöste
Strukturanalysde der extended spectrum Beta-Lactamase
CTX-M-14 (458246365) / 899 - ohne Topic (POF4-899)},
pid = {G:(GEPRIS)458246365 / G:(DE-HGF)POF4-899},
experiment = {EXP:(DE-MLZ)NOSPEC-20140101},
typ = {PUB:(DE-HGF)16},
doi = {10.1038/s42004-025-01801-x},
url = {https://bib-pubdb1.desy.de/record/642342},
}