Enzyme Evolution, Decoded by AlphaFold2

AlphaFold2 predicts protein structures with near-experimental accuracy, transforming the study of enzyme evolution across species. A recent study used AlphaFold2 to analyze metabolic enzymes from ancient to modern organisms, combining predicted and known structures to reveal how metabolism drives structural changes.

Enzyme evolution is shaped by reaction mechanisms, metal interactions, metabolic flux, and biosynthetic costs. Surface residues evolve fastest, while binding sites remain highly conserved. Key findings include:

• Visible evolutionary trajectories in structure space from small sequence changes
• Functional divergence linked to subtle structural shifts
• A visual map highlighting conserved functional regions amid adaptive changes

This work not only helps understand enzyme function but also uncovers their evolutionary history—showing that structure tells the story behind function.

More Reading

Lemke, O., et al. (2025). The role of metabolism in shaping enzyme structures over 400 million years. Nature. doi.org/10.1038/s41586-025-09205-6.