Discovery and Mechanistic Characterization of Selective Inhibitors of H₂S-producing Enzyme: 3-Mercaptopyruvate Sulfurtransferase (3MST) Targeting Active-site Cysteine Persulfide.

ABSTRACT: Very recent studies indicate that sulfur atoms with oxidation state 0 or -1, called sulfane sulfurs, are the actual mediators of some physiological processes previously considered to be regulated by hydrogen sulfide (H₂S). 3-Mercaptopyruvate sulfurtransferase (3MST), one of three H₂S-producing enzymes, was also recently shown to produce sulfane sulfur (H₂S_n). Here, we report the discovery of several potent 3MST inhibitors by means of high-throughput screening (HTS) of a large chemical library (174,118 compounds) with our H₂S-selective fluorescent probe, HSip-1. Most of the identified inhibitors had similar aromatic ring-carbonyl-S-pyrimidone structures. Among them, compound 3 showed very high selectivity for 3MST over other H₂

SUBMITTER: Hanaoka K 

PROVIDER: S-EPMC5228037 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature