Flavin adenine dinucleotide structural motifs: from solution to gas phase

Area of Science:

• Biochemistry
• Chemical Physics
• Spectroscopy

Background:

• Flavin adenine dinucleotide (FAD) is a vital cofactor in numerous metabolic enzymes.
• Its biological activity is closely linked to conformational flexibility.
• Understanding FAD's conformational states is key to elucidating its function.

Purpose of the Study:

• To investigate the conformational dynamics of FAD in solution and the gas phase.
• To correlate structural changes with environmental factors like solvent composition and gas-phase interactions.
• To provide insights into the molecular basis of FAD's functional versatility.

Main Methods:

• Fluorescence decay time measurements to probe solution conformations.
• Trapped Ion Mobility Spectrometry coupled with Mass Spectrometry (TIMS-MS) for gas-phase analysis.
• Density Functional Theory (DFT) calculations to model and validate observed structures.

Main Results:

• FAD exists in at least four conformations in solution, with extended forms favored by increased organic solvent content.
• Gas-phase FAD (deprotonated and protonated) displays up to 12 distinct conformations.
• Interactions with organic molecules in the gas phase induced a transition from 'stack' to 'close' conformations.

Conclusions:

• FAD's conformational landscape is significantly influenced by its environment, both in solution and the gas phase.
• The interplay between adenine and isoalloxazine rings, modulated by solvation effects, drives conformational stability.
• This study offers a comprehensive view of FAD's structural adaptability, relevant to its biological roles.