Density Functional Theory Investigation of As(III) S-Adenosylmethionine Methyltransferase

[Image: see text] Arsenic is one of the most pervasive environmental toxins. It enters our water and food supply through many different routes, including the burning of fossil fuels, the application of arsenic-based herbicides, and natural sources. Using a density functional theory (DFT) cluster approach, the mechanism of arsenic (III) S-adenosylmethionine methyltransferases and various selenium-containing analogues was investigated. Notably, the methylation of arsenic by arsenic (III) S-adenosylmethionine is proposed to be a way to remove arsenic from contaminated water or soil. From the DFT cluster results, it was found that the selective substitution of the active-site Cys44, Cys72, and Cys174 residues with selenocysteines had a marginal effect on the barrier for CH(3) transfer. Specifically, the average Gibbs activation energy was calculated to be only 4.2 kJ mol(–1) lower than the Gibbs activation energy of 107.4 kJ mol(–1) for the WT enzyme. However, importantly, it was found that with selective mutation, the methylation process becomes considerably more exergonic, where the methylation reaction can be made to be 26.4 kJ mol(–1) more exergonic than the reaction catalyzed by the WT enzyme. Therefore, we propose that the selective substitution of the active-site Cys44, Cys72 and Cys174 residues with selenocysteines could make the process of methylation and volatilization more advantageous for bioremediation.