Abstract
Noncovalent interactions between proteins and small-molecule ligands widely exist in biological bodies and play significant roles in many physiological and pathological processes. Native mass spectrometry (MS) has emerged as a new powerful tool to study noncovalent interactions by directly analyzing the ligand–protein complexes. In this work, an ultrahigh-resolution native MS method based on a 15-T SolariX XR Fourier transform ion cyclotron resonance mass spectrometer was firstly used to investigate the interaction between human serum albumin (HSA) and flavonoids. Various flavonoids with similar structure were selected to unravel the relationship between the structure of flavonoids and their binding affinity for HSA. It was found that the position of the hydroxyl groups and double bond of flavonoids could influence the noncovalent interaction. Through a competitive experiment between HSA binding site markers and apigenin, the subdomain IIA (site 1) of HSA was determined as the binding site for flavonoids. Moreover, a cooperative allosteric interaction between apigenin and ibuprofen was found from their different HSA binding sites, which was further verified by circular dichroism spectroscopy and molecular docking studies. These results show that native MS is a useful tool to investigate the molecular interaction between a protein and its ligands.
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We gratefully acknowledge the financial support of projects 21575142 and 21435006 by the National Natural Science Foundation of China.
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Published in the topical collection celebrating ABCs 16th Anniversary.
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Wang, B., Qin, Q., Chang, M. et al. Molecular interaction study of flavonoids with human serum albumin using native mass spectrometry and molecular modeling. Anal Bioanal Chem 410, 827–837 (2018). https://doi.org/10.1007/s00216-017-0564-7
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DOI: https://doi.org/10.1007/s00216-017-0564-7