Identification of Small Molecule Inhibitors of Human As(III) S-Adenosylmethionine Methyltransferase (AS3MT).

ABSTRACT: Arsenic is the most ubiquitous environmental toxin and carcinogen. Long-term exposure to arsenic is associated with human diseases including cancer, cardiovascular disease, and diabetes. Human As(III) S-adenosylmethionine (SAM) methyltransferases (hAS3MT) methylates As(III) to trivalent mono- and dimethyl species that are more toxic and potentially more carcinogenic than inorganic arsenic. Modulators of hAS3MT activity may be useful for the prevention or treatment of arsenic-related diseases. Using a newly developed high-throughput assay for hAS3MT activity, we identified 10 novel noncompetitive small molecule inhibitors. In silico docking analysis with the crystal structure of an AS3MT orthologue suggests that the inhibitors bind in a cleft between domains that is distant from either the

SUBMITTER: Dong H 

PROVIDER: S-EPMC4688878 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature