Open AccessStructure of the extended‐spectrum β‐lactamase TEM‐72 inhibited by citrate
Author(s) -
Docquier JeanDenis,
Benvenuti Manuela,
Calderone Vito,
Rossolini GianMaria,
Mangani Stefano
Publication year - 2011
Publication title -
acta crystallographica section f
Language(s) - English
Resource type - Journals
ISSN - 1744-3091
DOI - 10.1107/s1744309110054680
Subject(s) - serine , mutant , active site , broad spectrum , chemistry , enzyme , beta lactamase inhibitors , crystallography , stereochemistry , biochemistry , combinatorial chemistry , gene
TEM‐72, a class A β‐lactamase identified in isolates of Enterobacteriaceae , is a quadruple mutant of TEM‐1 (Q39K, M182T, G238S and E240K) and shows extended‐spectrum β‐lactamase (ESBL) properties arising from the G238S and E240K substitutions. Although many structures of TEM variants have been published, they do not include an enzyme with the simultaneous presence of both of the ESBL‐conferring G238S and E240K substitutions. Furthermore, the structure shows the presence of a citrate anion bound to the TEM‐72 active site, where it interacts with all of the conserved residues of class A β‐lactamases. The present structure supports the use of polycarboxylates as a scaffold for the design of broad‐spectrum inhibitors of serine β‐lactamases.