A QM/MM Study of Acylphosphatase Reveals the Nucleophilic-Attack and Ensuing Carbonyl-Assisted Catalytic Mechanisms

16 March 2020, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


Acylphosphatase is one of the vital enzymes in many organs/tissues to catalyze an acylphosphate molecule into carboxylate and phosphate. Here we use a combined ab initio QM/MM approach to reveal the catalytic mechanism of the benzoylphosphate-bound acylphosphatase system. Using a multi-dimensional reaction-coordinates-driving scheme, we obtained a detailed catalytic process including one nucleophilic-attack and then an ensuing carbonyl-shuttle catalytic mechanism by calculating two-dimensional potential energy surfaces. We also obtained an experiment-agreeable energy barrier and validated the role of the key amino acid Asn38. Additionally, we qualified the transition state stabilization strategy based on the amino acids-contributed interaction networks revealed in the enzymatic environment. This study provided usefule insights into the underlying catalytic mechanism to contribute to disease-involved research.


QM/MM study
Catalytic Mechanisms


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