A disulfide-bond cascade mechanism for arsenic(III) S-adenosylmethionine methyltransferase

Acta Crystallographica. Section D, Biological Crystallography
Kavitha MarapakalaBarry P Rosen

Abstract

Methylation of the toxic metalloid arsenic is widespread in nature. Members of every kingdom have arsenic(III) S-adenosylmethionine (SAM) methyltransferase enzymes, which are termed ArsM in microbes and AS3MT in animals, including humans. Trivalent arsenic(III) is methylated up to three times to form methylarsenite [MAs(III)], dimethylarsenite [DMAs(III)] and the volatile trimethylarsine [TMAs(III)]. In microbes, arsenic methylation is a detoxification process. In humans, MAs(III) and DMAs(III) are more toxic and carcinogenic than either inorganic arsenate or arsenite. Here, new crystal structures are reported of ArsM from the thermophilic eukaryotic alga Cyanidioschyzon sp. 5508 (CmArsM) with the bound aromatic arsenicals phenylarsenite [PhAs(III)] at 1.80 Å resolution and reduced roxarsone [Rox(III)] at 2.25 Å resolution. These organoarsenicals are bound to two of four conserved cysteine residues: Cys174 and Cys224. The electron density extends the structure to include a newly identified conserved cysteine residue, Cys44, which is disulfide-bonded to the fourth conserved cysteine residue, Cys72. A second disulfide bond between Cys72 and Cys174 had been observed previously in a structure with bound SAM. The loop containing Cys...Continue Reading

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Citations

Apr 24, 2016·Biomedical Journal·Hung-Chi Yang, Barry P Rosen
Oct 13, 2016·Metallomics : Integrated Biometal Science·Jiaojiao LiBarry P Rosen
Sep 13, 2018·Metallomics : Integrated Biometal Science·Changjun FanYong Cai
Feb 10, 2017·Oncotarget·Adam P SageVictor D Martinez
Aug 12, 2021·Microbiology Spectrum·Adriana E GalvánMasafumi Yoshinaga
Aug 25, 2020·Journal of Natural Products·Sazzad H SuzolMasafumi Yoshinaga
Sep 25, 2017·Environmental Science & Technology·Shashank S PawitwarMasafumi Yoshinaga
Dec 12, 2018·Environmental Science & Technology·Xi-Mei XueYong-Guan Zhu

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