TY - GEN
T1 - Pathways of arsenic biotransformations
T2 - 4th International Congress on Arsenic in the Environment, As 2012
AU - Rosen, B.
AU - Marapakala, K.
AU - Abdul Salam, A. A.
AU - Packianathan, C.
AU - Yoshinaga, M.
PY - 2012/8/16
Y1 - 2012/8/16
N2 - Arsenic methylation is catalyzed by the enzyme As(III)-S-adenosylmethionine methyltransferase (AS3MT or ArsM) that transfers up to three methyl groups from SAM to As(III), producing CH 3 As(III), (CH 3) 2MAs(III) and the nontoxic gaseous product (CH 3) 3MAs(III). In liver AS3MT methylates arsenic, which is excreted in urine. This biotransformation is thought to activate arsenic into a carcinogen. A thermophilic orthologue of human AS3MT was crystallized, and its x-ray crystal structure solved to 1.6 å with bound SAM or As(III). Our data support a pathway of methylation in which GSH conjugates are preferred substrates, and arsenic remains trivalent throughout the catalytic cycle. The location of polymorphisms were mapped onto a homology model of human AS3MT, giving insight into their biochemical effects. Finally, a new gene/enzyme that demethylates methylarsenicals was cloned/purified and characterized.
AB - Arsenic methylation is catalyzed by the enzyme As(III)-S-adenosylmethionine methyltransferase (AS3MT or ArsM) that transfers up to three methyl groups from SAM to As(III), producing CH 3 As(III), (CH 3) 2MAs(III) and the nontoxic gaseous product (CH 3) 3MAs(III). In liver AS3MT methylates arsenic, which is excreted in urine. This biotransformation is thought to activate arsenic into a carcinogen. A thermophilic orthologue of human AS3MT was crystallized, and its x-ray crystal structure solved to 1.6 å with bound SAM or As(III). Our data support a pathway of methylation in which GSH conjugates are preferred substrates, and arsenic remains trivalent throughout the catalytic cycle. The location of polymorphisms were mapped onto a homology model of human AS3MT, giving insight into their biochemical effects. Finally, a new gene/enzyme that demethylates methylarsenicals was cloned/purified and characterized.
UR - https://www.scopus.com/pages/publications/84864874053
UR - https://www.scopus.com/pages/publications/84864874053#tab=citedBy
M3 - Conference contribution
AN - SCOPUS:84864874053
SN - 9780415637633
T3 - Understanding the Geological and Medical Interface of Arsenic, As 2012 - 4th International Congress: Arsenic in the Environment
SP - 185
EP - 188
BT - Understanding the Geological and Medical Interface of Arsenic, As 2012 - 4th International Congress
Y2 - 22 July 2012 through 27 July 2012
ER -