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

preprint
submitted on 14.03.2020 and posted on 16.03.2020 by zheng zhao, Phil bourne, Hao Hu, Huanyu Chu
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.

History

Email Address of Submitting Author

zz7r@virginia.edu

Institution

Univeristy of Virginia

Country

U.S.A

ORCID For Submitting Author

0000-0003-1453-3230

Declaration of Conflict of Interest

no conflicts of interest

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