Format of Original
American Society for Biochemistry and Molecular Biology
Journal of Biological Chemistry
Original Item ID
Metallo-β-lactamases (MβLs) are zinc-dependent enzymes able to hydrolyze and inactivate most β-lactam antibiotics. The large diversity of active site structures and metal content among MβLs from different sources has limited the design of a pan-MβL inhibitor. Here we report the biochemical and biophysical characterization of a novel MβL, GOB-18, from a clinical isolate of a Gram-negative opportunistic pathogen, Elizabethkingia meningoseptica. Different spectroscopic techniques, three-dimensional modeling, and mutagenesis experiments, reveal that the Zn(II) ion is bound to Asp120, His121, His263, and a solvent molecule, i.e. in the canonical Zn2 site of dinuclear MβLs. Contrasting all other related MβLs, GOB-18 is fully active against a broad range of β-lactam substrates using a single Zn(II) ion in this site. These data further enlarge the structural diversity of MβLs.
Morrán-Barrio, Jorgelina; Gonzalez, Javier M.; Lisa, Mariá Natalia; Costello, Alison L.; Peraro, Matteo Dal; Carloni, Paolo; Bennett, Brian; Tierney, David L.; Limansky, Adriana S.; Viale, Alejandro M.; and Vila, Alejandro J., "The Metallo-β-lactamase GOB Is a Mono-Zn(II) Enzyme with a Novel Active Site" (2007). Physics Faculty Research and Publications. 91.
Published version. Journal of Biological Chemistry, Vol. 282, No. 25 (June 22, 2007): 18286-18293. DOI. © 2007 by The American Society for Biochemistry and Molecular Biology, Inc. Used with permission.
Brian Bennett was affiliated with the Medical College of Wisconsin at the time of publication.