Infrared Spectra of Beauvericin-Alkaline Earth Metal Ion Complexes─Ion Preference to Physiological Ions.

Beauvericin (Bv) is a naturally occurring ionophore that selectively transports ions through cell membranes. However, the intrinsic ion selectivity of Bv for alkaline earth metal ions (M2+) is yet to be established due to inconsistent results from condensed phase experiments. Based on fluorescence quenching rates, Ca2+ appears to be preferred while extraction experiments favor Mg2+. In this study, we apply cold ion trap─infrared spectroscopy to Bv-M2+ coupled with electrospray ionization mass spectrometry. The mass spectrum shows that Bv favors binding to physiologically active ions Mg2+ and Ca2+ although it can form complexes with all four alkaline earth metal ions. Infrared spectroscopy, as measured by the H2 tag technique, reveals that Bv binds Mg2+ and Ca2+ ions by six carbonyl oxygens in the center of its cavity. This observation is supported by theoretical calculations. Other alkaline earth metal ions are bound by three carbonyl groups at the amide face. This difference in configuration is consistent with the binding preferences for the alkaline earth metal ions.

Na+ Selective Binding by Beauvericin and Its Mechanism Studied by Mass-Coupled Cold Ion Trap Infrared Spectroscopy.

Beauvericin (Bv) is a cyclic hexadepsipeptide mycotoxin that selectively transports ions across cell membranes. Characterization of its intrinsic ion affinity has been complicated by different previous results in condensed phases and biological membranes. We report the marked specificity between alkali metal ions by Bv using experimental and computational methods. Mass spectrometry shows Bv readily binds all five alkali ions; however, the complex with Na+ is the most abundant species, indicating a strong binding preference. Gas phase infrared spectroscopy and theoretical calculations show that Li+, K+, Rb+, and Cs+ are coordinated by three amide carbonyl oxygens on the N-methylamino-l-phenylalanyl face. Selectivity for Na+ is achieved as Bv sequesters Na+ in the center of its cavity formed by three amide carbonyl and three ester carbonyl groups, a configuration unique among alkali metal ions. This finding provides insight into the correlation between selectivity and conformation of Bv, essential for development of this mycotoxin.