9EU0
Crystal structure of Danio rerio HDAC6 CD2 in complex with hydrolyzed DFMO-inhibitor (ITF7209)
This is a non-PDB format compatible entry.
Summary for 9EU0
| Entry DOI | 10.2210/pdb9eu0/pdb |
| Descriptor | Histone deacetylase 6, ZINC ION, POTASSIUM ION, ... (6 entities in total) |
| Functional Keywords | histone deacetylase, complex with hydrazide, hydrolase, non-hydroxamate zinc binding group, mechanism-based inhibitor |
| Biological source | Danio rerio (zebrafish) |
| Total number of polymer chains | 2 |
| Total formula weight | 81925.34 |
| Authors | Bebel, A.,Cellupica, E.,Stevenazzi, A.,Sandrone, G.,Vergani, B.,Caprini, G. (deposition date: 2024-03-27, release date: 2024-12-04) |
| Primary citation | Cellupica, E.,Gaiassi, A.,Rocchio, I.,Rovelli, G.,Pomarico, R.,Sandrone, G.,Caprini, G.,Cordella, P.,Cukier, C.,Fossati, G.,Marchini, M.,Bebel, A.,Airoldi, C.,Palmioli, A.,Stevenazzi, A.,Steinkuhler, C.,Vergani, B. Mechanistic and Structural Insights on Difluoromethyl-1,3,4-oxadiazole Inhibitors of HDAC6. Int J Mol Sci, 25:-, 2024 Cited by PubMed Abstract: Histone deacetylase 6 (HDAC6) is increasingly recognized for its potential in targeted disease therapy. This study delves into the mechanistic and structural nuances of HDAC6 inhibition by difluoromethyl-1,3,4-oxadiazole (DFMO) derivatives, a class of non-hydroxamic inhibitors with remarkable selectivity and potency. Employing a combination of nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography-mass spectrometry (LC-MS) kinetic experiments, comprehensive enzymatic characterizations, and X-ray crystallography, we dissect the intricate details of the DFMO-HDAC6 interaction dynamics. More specifically, we find that the chemical structure of a DMFO and the binding mode of its difluoroacetylhydrazide derivative are crucial in determining the predominant hydrolysis mechanism. Our findings provide additional insights into two different mechanisms of DFMO hydrolysis, thus contributing to a better understanding of the HDAC6 inhibition by oxadiazoles in disease modulation and therapeutic intervention. PubMed: 38892072DOI: 10.3390/ijms25115885 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.86 Å) |
Structure validation
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