Acetate kinase: a triple-displacement enzyme.

Area of Science:

• Biochemistry
• Enzymology
• Protein Mechanisms

Background:

• Acetate kinase (ATP:acetate phosphotransferase, EC 2.7.2.1) catalyzes essential phosphoryl transfer reactions.
• Previous studies suggest the involvement of at least one phosphoenzyme (E-P) intermediate in the enzymatic mechanism.
• The stereochemical outcome of phosphoryl transfer reactions is crucial for understanding enzyme mechanisms.

Purpose of the Study:

• To review and analyze existing data on the mechanism of phosphoryl transfer by acetate kinase.
• To elucidate the precise mode of action and the number of phosphoenzyme intermediates involved.
• To reconcile experimental observations with proposed reaction mechanisms.

Main Methods:

• Literature review of experimental data on acetate kinase.
• Analysis of stereochemical evidence related to phosphoryl transfer.
• Theoretical evaluation of proposed reaction pathways.

Main Results:

• Evidence supports the existence of at least one experimentally established phosphoenzyme (E-P) intermediate.
• Phosphoryl transfer by acetate kinase proceeds with a net inversion of phosphorus atom configuration.
• A triple-displacement mechanism, involving two E-P intermediates and three steric inversions, best explains the observed data.

Conclusions:

• The findings strongly suggest a second, previously uncharacterized, phosphoenzyme (E-P) intermediate for acetate kinase.
• The triple-displacement model provides a comprehensive framework for acetate kinase's phosphoryl transfer mechanism.
• Further experimental validation is warranted to confirm the existence and role of the second E-P intermediate.