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

Kai Cheng; Qiong Wu; Chendie Yao; Zhaofei Chai; Ling Jiang; Maili Liu; Conggang Li

doi:10.1021/jacsau.2c00651

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

JACS Au. 2023 Feb 27;3(3):849-859. doi: 10.1021/jacsau.2c00651. eCollection 2023 Mar 27.

Authors

Kai Cheng¹, Qiong Wu¹, Chendie Yao¹, Zhaofei Chai¹, Ling Jiang^{1

2}, Maili Liu^{1

2}, Conggang Li^{1

2}

Affiliations

¹ Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy of Precision Measurement, Chinese Academy of Sciences, Wuhan 430071, China.
² Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan 430074, China.

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.