Transferases;
Transferring one-carbon groups;
Methyltransferases
BRITE hierarchy

S-adenosyl-L-methionine:arsenous acid As-methyltransferase

(1) S-adenosyl-L-methionine + arsenic triglutathione + thioredoxin + 2 H2O = S-adenosyl-L-homocysteine + methylarsonous acid + 3 glutathione + thioredoxin disulfide [RN:R12917];
(2) 2 S-adenosyl-L-methionine + arsenic triglutathione + 2 thioredoxin + H2O = S-adenosyl-L-homocysteine + dimethylarsinous acid + 3 glutathione + 2 thioredoxin disulfide [RN:R12918];
(3) 3 S-adenosyl-L-methionine + arsenic triglutathione + 3 thioredoxin = S-adenosyl-L-homocysteine + trimethylarsane + 3 glutathione + 3 thioredoxin disulfide [RN:R12919]

R12917 R12918 R12919
Reaction

S-adenosyl-L-methionine [CPD:C00019];
arsenic triglutathione [CPD:C22431];
thioredoxin [CPD:C00342];
H2O [CPD:C00001]

An enzyme responsible for synthesis of trivalent methylarsenical antibiotics in microbes [11] or detoxification of inorganic arsenous acid in animals. The in vivo substrate is arsenic triglutathione or similar thiol (depending on the organism) [6], from which the arsenic is transferred to the enzyme forming bonds with the thiol groups of three cysteine residues [10] via a disulfide bond cascade pathway [7, 8]. Most of the substrates undergo two methylations and are converted to dimethylarsinous acid [9]. However, a small fraction are released earlier as methylarsonous acid, and a smaller amount proceeds via a third methylation, resulting in the volatile product trimethylarsane. Methylation involves temporary oxidation to arsenic(V) valency, followed by reduction back to arsenic(III) valency using electrons provided by thioredoxin or a similar reduction system. The arsenic(III) products are quickly oxidized in the presence of oxygen to the corresponding arsenic(V) species.

EC 2.1.1.137 created 2000, (EC 2.1.1.138 incorporated 2003), modified 2003, modified 2021