9mqp | pdb_00009mqp

Crystal structure of Danio rerio histone deacetylase 6 catalytic domain 2 complexed with SelSA

spinqualitylabelsall models 9mqp, resolution 2.15Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9mqp is a 2 chain structure with sequence from Danio rerio. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.15Å Ligands: A1BNN, EDO, K, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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