A Lysine-Targeted Affinity Label for Serine-β-Lactamase Also Covalently Modifies New Delhi Metallo-β-lactamase-1 (NDM-1).

ABSTRACT: The divergent sequences, protein structures, and catalytic mechanisms of serine- and metallo-β-lactamases hamper the development of wide-spectrum β-lactamase inhibitors that can block both types of enzymes. The O-aryloxycarbonyl hydroxamate inactivators of Enterobacter cloacae P99 class C serine-β-lactamase are unusual covalent inhibitors in that they target both active-site Ser and Lys residues, resulting in a cross-link consisting of only two atoms. Many clinically relevant metallo-β-lactamases have an analogous active-site Lys residue used to bind β-lactam substrates, suggesting a common site to target with covalent inhibitors. Here, we demonstrate that an O-aryloxycarbonyl hydroxamate inactivator of serine-β-lactamases can also serve as a classical affinity label for New Delhi metallo-

SUBMITTER: Thomas PW 

PROVIDER: S-EPMC6597302 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature