TY  - JOUR
AU  - Gore, Gargi
AU  - Prester, Andreas
AU  - von Stetten, David
AU  - Bartels, Kim
AU  - Schulz, Eike C.
TI  - Binding mode of Isoxazolyl Penicillins to a Class-A β-lactamase at ambient conditions
JO  - Communications chemistry
VL  - 8
IS  - 1
SN  - 2399-3669
CY  - [London]
PB  - Macmillan Publishers Limited, part of Springer Nature
M1  - PUBDB-2025-05497
SP  - 387
PY  - 2025
AB  - 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. 
LB  - PUB:(DE-HGF)16
DO  - DOI:10.1038/s42004-025-01801-x
UR  - https://bib-pubdb1.desy.de/record/642342
ER  -