Probing Interaction Between Meropenem and NDM-1 by Multispectral Method and Molecular Dynamic Simulation
LI Jia-chen1, LI Na1, LIU Di1, ZHANG Jia-xin2, CHENG Jian-wei3, ZHANG Ye-li1, 3*
1. College of Biological Sciences and Technology, Taiyuan Normal University, Jinzhong 030619, China
2. College of Life Science, Northwest University, Xi'an 710069, China
3. Shanxi Key Laboratory of Earth Surface Processes and Resource Ecological Security in Fenhe River Basin, School of Geography Science, Taiyuan Normal University, Jinzhong 030619, China
Abstract：The emergence and worldwide spread of metallo-β-lactamase-producing bacteria, particularly New Delhi metallo-β-lactamase (NDM-1), has poseda tremendous challenge in treating drug-resistant bacterial infections. It hydrolyzes almost all β-lactam antimicrobial agents, coupled with the absence of clinically available inhibitors. To comprehend the molecular recognition and interaction between NDM-1 and β-lactam antimicrobial agents, the interaction between NDM-1 and meropenem (MER) was probed by quenching spectroscopy, synchronous fluorescence spectroscopy, circular dichroism spectroscopy, and molecular dynamics simulation. Quenching spectroscopy revealed that MER could cause NDM-1 to undergo endogenous fluorescence quenching and affect the microenvironment of approximately one Trp residue of NDM-1.Synchronous fluorescence spectroscopy displayed that the maximum emission wavelengths of NDM-1 were blue-shifted by 4.0 and 2.0 nm, implying that both Tyr and Trp residues were involved in the binding. Circular dichroism spectroscopy exhibited that the secondary structure of NMD-1 was changed after its interaction with MER, with a decrease in β-sheets, and an increase in irregularly coiled content, suggesting a flexible binding process. In the molecular dynamics results, the β4 (40-47) located near the active pocket of NDM-1 adopted an irregular coil conformation, and loop2 exhibited substantial fluctuations, facilitating NDM-1-MER induced fit. The induced fit effect between NDM-1 and MER was consistent with synchrotron fluorescence and circular dichroism spectroscopy results. Trp93 and His250 amino acid residues formed hydrophobic interactions with MER at the side-chain amino group and the methyl group of the β-lactam ring, respectively, and the amino acid residues of Ile35, Val73, Ala74, Gly36, and Met67 formed van der Waals forces with MER, further promoting the binding. This present study gives crucialinsights into the molecular recognition process of NDM-1 with MER, which may provide new perspectives and a theoretical basis for future development of novel antibiotics and inhibitors targeting this clinically important resistance mechanism.
李嘉晨，李 娜，刘 地，张嘉昕，程建伟，张椰莉. 多光谱法与计算机模拟探究美罗培南与NDM-1之间的相互作用[J]. 光谱学与光谱分析, 2025, 45(08): 2386-2392.
LI Jia-chen, LI Na, LIU Di, ZHANG Jia-xin, CHENG Jian-wei, ZHANG Ye-li. Probing Interaction Between Meropenem and NDM-1 by Multispectral Method and Molecular Dynamic Simulation. SPECTROSCOPY AND SPECTRAL ANALYSIS, 2025, 45(08): 2386-2392.
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