Functional evaluation of Asp76, 84, 102 and 150 in human arsenic(III) methyltransferase (hAS3MT) interacting with S-adenosylmethionine

• hAS3MT mutants D76P, D76N, D84P, D84N, D102P, D102N, D150P and D150N were designed.
• All mutants except for D150N were inactive.
• Asp76, 84, 102 and 150 of hAS3MT greatly affected hAS3MT catalytic activity.
• Asp102 plays a dominant role in SAM-binding via forming hydrogen bonds with SAM.

We prepared eight mutants (D76P, D76N, D84P, D84N, D102P, D102N, D150P and D150N) to investigate the functions of residues Asp76, 84, 102 and 150 in human arsenic(III) methyltransferase (hAS3MT) interacting with the S-adenosylmethionine (SAM)-binding. The affinity of all the mutants for SAM were weakened. All the mutants except for D150N completely lost their methylation activities. Residues Asp76, 84, 102 and 150 greatly influenced hAS3MT catalytic activity via affecting SAM-binding or methyl transfer. Asp76 and 84 were located in the SAM-binding pocket, and Asp102 significantly affected SAM-binding via forming hydrogen bonds with SAM.