Hormesis of some organic solvents on Vibrio qinghaiensis sp.-Q67 from first binding to the β subunit of luciferase

Hormesis is a biphasic concentration-response relationship. During the luminescence inhibition test of Vibrio qinghaiensis sp.-Q67 (Q67), some organic solvents display the hormesis phenomenon. However, the mechanism of hormesis with respect to organic solvents remains unclear. This study focuses on luciferase, which is the key factor in luminescent reactions, and explores its role in the mechanism of hormesis. Q67 luciferase has two subunits, alpha and beta. Molecular docking and molecular dynamics simulations were carried out by taking organic solvents as ligand and the two subunits as receptor. In addition, the binding free energies of the complexes formed by the ligand and Q67 luciferase were calculated. The results showed that the organic solvent ligands exhibiting hormesis bind to the beta subunit first, while those that do not exhibit hormesis bind more easily to the alpha subunit. The hormetic organic solvents bind to beta subunit first at low concentration, and change the flexibility of residues Ser145-Arg165 located on the alpha subunit; this enables flavin mononucleotide (FMN) to bind to the alpha subunit, exhibiting the hormesis phenomenon. With the increasing concentration, redundant molecules start to bind to the alpha subunit and compete with/block FMN binding to the alpha subunit, resulting in inhibition.