Luminescence Activity Decreases When v ‐Coelenterazine Replaces Coelenterazine in Calcium‐regulated Photoprotein – A Theoretical and Experimental Study

AbstractCalcium ‐regulated photoprotein is found in at least five phyla of organisms. The light emitted by those photoproteins can be tuned by mutating the photoprotein and/or by modifying the substrate coelenterazine (CTZ). Thirty years ago, Shimomura observed that the luminescence activity of aequorin was drama tically reduced when the substrate CTZ was replaced by its analogv‐CTZ. The latter is formed by adding a phenyl ring to the π‐conjugated moiety of CTZ. The decrease in luminescence activity has not been understood until now. In this paper, through combined quantum mechanics and molecular mechanics calculations as well as molecular dynamics simulations, we dis covered the reason for this observation. Modification of the substrate changes the conformation of nearby aromatic residues and enhances the π‐π stacking interactions between the conjugated moiety ofv‐CTZ and the residues, which weakens the charge transfer to form light emitter and leads to a lower luminescence activity. The microenvironments of CTZ in obelin and in aequorin are very similar, so we predicted that the luminescence activity of obelin will also dramatically decrease when CTZ is r eplaced byv‐CTZ. This prediction has received strong evidence from currently theoretical calculations and has been verified by experiments.

Source: Photochemistry and Photobiology - May 15, 2020 Category: Science Authors: Bo ‐Wen Ding, Elena V. Eremeeva, Eugene S. Vysotski, Ya‐Jun Liu Tags: RESEARCH ARTICLE Source Type: research