Crystal structure of a preacylation complex of the β-lactamase inhibitor sulbactam bound to a sulfenamide bond-containing thiol-β-lactamase.

ABSTRACT: The rise of inhibitor-resistant and other β-lactamase variants is generating an interest in developing new β-lactamase inhibitors to complement currently available antibiotics. To gain insight into the chemistry of inhibitor recognition, we determined the crystal structure of the inhibitor preacylation complex of sulbactam, a clinical β-lactamase inhibitor, bound in the active site of the S70C variant of SHV-1 β-lactamase, a resistance enzyme that is normally present in Klebsiella pneumoniae. The S70C mutation was designed to affect the reactivity of that catalytic residue to allow for capture of the preacylation complex. Unexpectedly, the 1.45 Å resolution inhibitor complex structure revealed that residue C70 is involved in a sulfenamide bond with K73. Such a covalent bond is not present

SUBMITTER: Rodkey EA 

PROVIDER: S-EPMC4037319 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature