Skip to main content
. Author manuscript; available in PMC: 2019 Jul 17.
Published in final edited form as: Biochemistry. 2018 Jun 26;57(28):4083–4092. doi: 10.1021/acs.biochem.8b00457

Figure 8.

Figure 8.

Initial steps in the methylation pathway. The first four steps of the pathway leading to methylation of As(III) to MAs(III). In step 1, As(III) is bound to Cys44, Cys174, and Cys224. In step 2, As(III) is oxidatively methylated to form a hypothetical pentavelent intermediate. In step 3, the transient pentavelent intermediate is reduced to enzyme-bound MAs(III) bound to Cys174 and Cys224 with electrons from Cys72, which forms a disulfide bond with Cys44. In step 4, the disulfide bond is reduced by thioredoxin. The bottom panels show structures related to the first four steps: (1) As(III)/SAH-bound CmArsM (PDB entry 6CX6), showing As(III) bound to Cys44, Cys174, and Cys224; (2) SAM-bound CmArsM (PDB entry 4FR0), showing the orientation of the S-methyl group toward the arsenic binding site; (3) formation of the Cys44−Cys72 disulfide bond (PDB entry 4KW7); and (4) the reduced disulfide bond, regenerating Cys44 and Cys72, in MAs(III)-bound CmArsM (PDB entry 5JWN).