Structural insights into the evolution of alpha/beta-hydrolase fold luciferases
| Authors | |
|---|---|
| Year of publication | 2026 |
| Type | Peer-reviewed scientific article |
| Magazine / Source | International journal of biological macromolecules |
| MU Faculty or unit | |
| Citation | |
| web | https://www.sciencedirect.com/science/article/pii/S0141813026017964 |
| Doi | https://doi.org/10.1016/j.ijbiomac.2026.151870 |
| Keywords | alpha/(3-hydrolase fold; Bioluminescence; Catalysis; Evolution; Haloalkane dehalogenase; Luciferase |
| Attached files | |
| Description | The alpha/(3-hydrolase (ABH) superfamily is a widespread and functionally versatile protein fold recognized for its ability to adapt to diverse molecular functions across all three domains of life. One such spectacular example of evolutionary adaptation at the ABH fold is an acquisition of oxygenolytic luciferase reaction that occurred within the hydrolytic haloalkane dehalogenase family. The molecular details of this evolution remain puzzling. In this work, we determine crystal structures and explore dynamical behaviour of a bifunctional ancestral ABH-fold enzyme, highlighting molecular features associated with the transition from hydrolytic to oxygenolytic catalysis at this fold. Structures showed a canonical alpha(3 alpha-sandwich shielded with a helical cap domain. The catalytic pocket is voluminous enough to accommodate a bulky substrate. Molecular dynamics simulations demonstrated that coelenterazine entry does not present a major energetic barrier and identified a preferred binding orientation important for oxygenolytic catalysis. Comparisons between ancestral and extant enzymes highlighted specific amino acids and sequence motifs characteristic for oxygenolytic luciferases. Collectively, our results provide an expanded view of the evolutionary transition in which ABH-fold enzymes, originally using water to cleave chemical bonds, adapted to utilize dioxygen for bioluminescence. |
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