%0 Journal Article
%A Gore, Gargi
%A Prester, Andreas
%A von Stetten, David
%A Bartels, Kim
%A Schulz, Eike C.
%T Binding mode of Isoxazolyl Penicillins to a Class-A β-lactamase at ambient conditions
%J Communications chemistry
%V 8
%N 1
%@ 2399-3669
%C [London]
%I Macmillan Publishers Limited, part of Springer Nature
%M PUBDB-2025-05497
%P 387
%D 2025
%X 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. 
%F PUB:(DE-HGF)16
%9 Journal Article
%R 10.1038/s42004-025-01801-x
%U https://bib-pubdb1.desy.de/record/642342