Arsenic methyltransferase, also known as arsenite methyltransferase (AS3MT), is an enzyme that plays a crucial role in the biomethylation of arsenic. This enzyme is responsible for the conversion of inorganic arsenic into its methylated forms, which are generally less toxic and more easily excreted from the body. The human recombinant form of this enzyme is often used in research to study its structure, function, and role in arsenic metabolism.
The human AS3MT gene encodes a protein consisting of 375 amino acids with a molecular weight of approximately 41.7 kDa . This enzyme contains several cysteine residues that are essential for its catalytic activity. The cysteine residues form disulfide bonds, which are crucial for the enzyme’s function. For instance, the disulfide bond between Cys250 and Cys32 is reduced by glutathione (GSH) or other reductants before the enzymatic methylation of arsenite .
AS3MT catalyzes the transfer of a methyl group from S-adenosyl-L-methionine (AdoMet) to arsenic, producing monomethyl and dimethyl arsenicals . The enzyme’s active site binds to arsenite (iAs^3+) and facilitates its methylation. The methylation process involves the formation of intermediate complexes, such as Cys250-S-adenosylhomocysteine (AdoHcy), which suggests that Cys250 is involved in the transmethylation process .
Arsenic is a ubiquitous environmental contaminant that poses significant health risks. The methylation of arsenic by AS3MT is a critical detoxification pathway that reduces the toxicity of arsenic and enhances its excretion. The methylated forms of arsenic, such as monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), are less toxic and more water-soluble, facilitating their elimination from the body.
Recombinant human AS3MT is widely used in research to understand the molecular mechanisms of arsenic methylation and its implications for human health. Studies have shown that mutations in the AS3MT gene can affect the enzyme’s activity and influence an individual’s susceptibility to arsenic toxicity . Additionally, research on AS3MT has provided insights into the role of glutathione and other reductants in the methylation process .