Page 190 - Arrow Pushing in Inorganic Chemistry A Logical Approach to the Chemistry of the Main Group Elements

THE HEAVIER PNICTOGENS
170
OH CH 3 CH 3 CH 3
+ − + − + +
As As As − As −
O O O O
HO HO HO H C
OH OH CH 3 3 CH 3
Arsenate Methylarsonate Dimethylarsinate Trimethylarsine oxide
Reduction Methylation Reduction Methylation Reduction Methylation Reduction

OH CH 3 CH 3 CH 3

As As As As
HO HO HO H 3 C
HO HO H 3 C H 3 C
Arsenite Methylarsonite Dimethylarsinite Trimethylarsine
Challenger model for arsenic biomethylation.
Figure 5B.1

C224
SAM
As
4.50
Cl 4.22
C174 5.80
5.00
C72

Crystallographic model of a ternary complex of CmArsM, SAM, and trivalent As.
Figure 5B.2
Selected distances (Å) from the S-methyl carbon of SAM are shown as dotted lines. (This figure is
adapted from Qin, J., et al. Proc. Natl. Acad. Sci. USA 2009, 106, 5213–5217.)

Enzymes catalyzing the transfer of methyl groups from SAM to trivalent arsenic, called
AS3MT, an abbreviation for As(III) SAM methyltransferase, occur in all the kingdoms
of life, from bacteria to humans. Crystal structures of such an enzyme (CmArsM)
extracted from the thermoacidophilic eukaryotic red alga Cyanidioschyzon merolae from
Yellowstone National Park have shed significant light on the biomethylation process.
A model based on multiple crystal structures of CmArsM (Figure 5B.2) shows an
arsenic atom coordinated by two cysteine sulfurs, with a third uncoordinated cysteine
nearby. The methyl group of the SAM is also perfectly aligned for S 2 attack by the
N
trivalent As.
Although there is broad consensus that methylation acts as a detoxification mechanism
in arsenic-tolerant bacteria, the physiological role of human AS3MT is less clear, because
methylated trivalent arsenic species are potent carcinogens.