Beneficial mutations of enzymes far from active site improve substrate binding and product release

Summary

Mutations that are beneficial for enzymes that are far from the active site tune conformational dynamics to improve substrate binding and substrate release (1). However, they do not “compensate” for destabilizing active site mutations as was previously hypothesized. This was shown using Kemp eliminase.

See also

• Rigidification of active site residues accelerates enzyme activity

1.

Zarifi N, Asthana P, Doustmohammadi H, Klaus C, Sanchez J, Hunt SE, et al. Distal mutations enhance catalysis in designed enzymes by facilitating substrate binding and product release. Nature Communications. 2025;16(1). Available from: https://doi.org/10.1038/s41467-025-63802-7