Sunday, July 24, 2011
Grand Ballroom, 5th fl (Sheraton New Orleans)
Arsenic ranks first on the Environmental Protection Agency's Superfund Priority List of Hazardous Chemicals due to combination of its ubiquity and effects on human health. A common biotransformation of arsenic is methylation to mono-, di- and trimethylated species. Methylation is catalyzed by the enzyme As(III) S-adenosylmethionine methyltransferase, an enzyme (ArsM or AS3MT) (EC 2.1.1.137) that is found in members of every kingdom from bacteria to humans. ArsM from the thermophilic alga Cyanidioschyzon sp. 5508 was expressed, purified and crystallized. The crystals belonged to the monoclinic space group C2, with unit-cell parameters a=84.85Å, b=46.89Å, c=100.35Å, β =114.25º degrees, with one molecule in the asymmetric unit. Here we report the crystal structures of ArsM, in complex with SAM (S-adenosyl-L-methionine) or in complex with arsenite at 1.6 Å, 2.55 Å, 1.6 Å, respectively. The crystal structure shows that ArsM is a multimodular protein composed of 3 domains, an N-terminal SAM binding domain, an arsenic binding and a C-terminal domain of unknown function. A single tryptophan derivative of ArsM was constructed in which the tryptophan is near the As(III) binding site. From the effect of ligands on protein fluorescence, we propose that the initial substrate of ArsM is As(GS)3, the triglutathione conjugate of As(III).
(Supported by NIH grant R37 GM55425).