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Poster Presentations
Day 2, June 23（Mon.）
Room P (Maesato East, Foyer, Ocean Wing)
- 2P-AM-28
Conformational Dynamics of Beta-Lactamase by Hydrogen Deuterium Exchange Mass Spectrometry
(1CPS-ZJU, 2ABCT-HKPU)
oLi-Wen Huang1, Zhong-Ping Yao2
Metallo-beta-lactamases (MBLs) are a global threat due to their ability to hydrolyze beta-lactam antibiotics, undermining last-resort therapies. This study examines how single mutations in NDM-β-lactamases enhance antibiotic resistance. Using hydrogen/deuterium exchange mass spectrometry (HDX-MS), we analyzed the conformational dynamics of NDM-1 with inhibitors like L/D-captopril, Ebselen, and Aspergillomarasmine A (AMA). Results revealed inhibitor-specific conformational changes, particularly in the active-site loop (ASL) regions, with significant alterations in the rarely studied L8 region. The M154L mutation in L8 impacted ASL dynamics, showing minimal effects on L/D-captopril binding but marked differences with Ebselen and AMA compared to wild-type NDM-1. These findings suggest Zn sequestration induces conformational rearrangements in M154L mutants, enhancing resistance. This study provides mechanistic insights into how single mutations rewire NDM-1 dynamics, highlighting the L8 region as a potential target for mechanism-based inhibitors. These discoveries offer new avenues for combating MBL-mediated resistance.