Mapping Strigolactone Hydrolysis in DWARF14 via QM/MM String Method

Area of Science:

• Plant biology
• Biochemistry
• Molecular signaling

Background:

• Strigolactone signaling is unique as the DWARF14 (D14) receptor hydrolyzes the hormone.
• Unresolved questions include the hydrolysis mechanism and the nature of the activation-inducing modification.

Purpose of the Study:

• To elucidate the mechanism of strigolactone hydrolysis by the D14 receptor.
• To identify the covalent modifications that activate the receptor.

Main Methods:

• Utilized Quantum Mechanics/Molecular Mechanics (QM/MM) string method simulations.
• Simulated the D14-GR24 complex to analyze reaction pathways.

Main Results:

• The canonical acyl substitution pathway, initiated by nucleophilic attack on the butenolide (D-ring), is strongly favored.
• Multiple, interconverting covalent adducts form between the butenolide ring and catalytic residues.

Conclusions:

• Hydrolysis proceeds via a favored canonical acyl substitution mechanism.
• Receptor activation involves a dynamic ensemble of covalent modifications, not a single static species.
• Provides a mechanistic framework reconciling experimental data on strigolactone signaling.