9MQP
Crystal structure of Danio rerio histone deacetylase 6 catalytic domain 2 complexed with SelSA
This is a non-PDB format compatible entry.
Summary for 9MQP
| Entry DOI | 10.2210/pdb9mqp/pdb |
| Descriptor | Hdac6 protein, N-phenyl-6-selanylhexanamide, 1,2-ETHANEDIOL, ... (6 entities in total) |
| Functional Keywords | hydrolase, histone deacetylase, selenol, inhibitor, metallohydrolase |
| Biological source | Danio rerio (zebrafish) |
| Total number of polymer chains | 2 |
| Total formula weight | 81522.77 |
| Authors | Goulart Stollmaier, J.,Czarnecki, B.A.R.,Christianson, D.W. (deposition date: 2025-01-04, release date: 2025-03-05, Last modification date: 2025-03-12) |
| Primary citation | Goulart Stollmaier, J.,Czarnecki, B.A.R.,Christianson, D.W. Mechanism-Based Inhibition of Histone Deacetylase 6 by a Selenocyanate Is Subject to Redox Modulation. J.Am.Chem.Soc., 147:6373-6377, 2025 Cited by PubMed Abstract: 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 Å-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. PubMed: 39957581DOI: 10.1021/jacs.5c00157 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.15 Å) |
Structure validation
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