Structural highlights
Function
A7YT55_DANRE
Publication Abstract from PubMed
Organoselenocyanates have attracted considerable attention in recent years due to their therapeutic potential and versatility in medicinal chemistry. Here, we report on the mechanism of inhibition by 5-phenylcarbamoylpentyl selenocyanide (SelSA-2), an analogue of the well-characterized histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA, a.k.a. Vorinostat). We show that histone deacetylases 6 and 10 promote selenocyanate hydrolysis to generate a selenolate anion, and we explore the redox chemistry of selenium as it modulates inhibitory activity through reversible formation of the diselenide. The 2.15 A-resolution crystal structure of histone deacetylase 6 cocrystallized with SelSA-2 conclusively demonstrates that it is not the selenocyanate, but instead a zinc-bound selenolate anion, that is the active pharmacophore responsible for enzyme inhibition.
Mechanism-Based Inhibition of Histone Deacetylase 6 by a Selenocyanate Is Subject to Redox Modulation.,Goulart Stollmaier J, Czarnecki BAR, Christianson DW J Am Chem Soc. 2025 Feb 26;147(8):6373-6377. doi: 10.1021/jacs.5c00157. Epub 2025 , Feb 17. PMID:39957581[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Goulart Stollmaier J, Czarnecki BAR, Christianson DW. Mechanism-Based Inhibition of Histone Deacetylase 6 by a Selenocyanate Is Subject to Redox Modulation. J Am Chem Soc. 2025 Feb 26;147(8):6373-6377. PMID:39957581 doi:10.1021/jacs.5c00157
