Distinct Inhibition Modes of New Delhi Metallo-β-lactamase-1 Revealed by NMR Spectroscopy

Abstract

The wide spread of antibiotic-resistant “superbugs” containing New Delhi metallo-β-lactamase-1 (NDM-1) has become a threat to human health. However, clinically valid antibiotics to treat the superbugs’ infection are not available now. Quick, simple, and reliable methods to assess the ligand-binding mode are key to developing and improving inhibitors against NDM-1. Herein, we report a straightforward NMR method to distinguish the NDM-1 ligand-binding mode using distinct NMR spectroscopy patterns of apo- and di-Zn-NDM-1 titrations with various inhibitors. Elucidating the inhibition mechanism will aid the development of efficient inhibitors for NDM-1.