Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Your Environment. Your Health.

Publication Detail

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

Authors: Dong, Hui; Madegowda, Mahendra; Nefzi, Adel; Houghten, Richard A; Giulianotti, Marc A; Rosen, Barry P

Published In Chem Res Toxicol, (2015 Dec 21)

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 As(III) or SAM binding sites. This suggests the presence of a possible allosteric and regulatory site in the enzyme. These inhibitors may be useful tools for future research in arsenic metabolism and are the starting-point for the development of drugs against hAS3MT.

PubMed ID: 26577531 Exiting the NIEHS site

MeSH Terms: Arsenic*/chemistry; Binding Sites; Biological Assay; Crystallography, X-Ray; Drug Evaluation, Preclinical; Enzyme Activation/drug effects; Enzyme Inhibitors/pharmacology; Humans; Methyltransferases/antagonists & inhibitors*; Methyltransferases/chemistry; Molecular Docking Simulation; S-Adenosylmethionine*/chemistry; Small Molecule Libraries/chemistry; Small Molecule Libraries/pharmacology*

Back
to Top