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Poster Presentations
Day 3, June 24（Tue.）
Room P (Maesato East, Foyer, Ocean Wing)
- 3P-PM-31
Understanding Enzyme-Inhibitor Interactions via Native Mass Spectrometry
(1Zhejiang Univ., 2HUST)
oMowei Zhou1, Shiwen Zhou1, Beiyao Fu1, Xinjie Yang2, Pengfei Ji1, Fangrui Zhong2, Yuanjiang Pan1
Driven by artificial intelligence, computational advancements such as AlphaFold have paved new pathways for the rapid engineering of functional enzymes. However, experimental validation still largely depends on high-throughput screening (HTS) to acquire functional and phenotypic data, with mechanistic structural data reserved for only a few selected candidates due to the low throughput of current methods. Native mass spectrometry (native MS) provides rapid characterization of molecular structures and interactions, potentially enriching the existing toolbox of experimental HTS methods to refine computational models. This is particularly valuable by extracting mechanistic insights into molecular structural features from "failed" designs. Nevertheless, further fundamental research and methodological advancements are crucial to accurately correlate subtle structural features with native MS data. Herein, we investigate the interaction of an artificial triplet photoenzyme, RamR, with two quenchers, which inhibit the enzyme to varying degrees, presumably through distinct binding mechanisms. Native MS indicates that both quenchers directly interact with the enzyme with different charging behaviors. However, the binding appears non-selective on the protein surface, lacking a well-defined site and stoichiometry. Ongoing experiments aim to further examine the enzyme-inhibitor interaction in the presence of the native substrate, to provide more informed guidance for future enzyme designs.