9eu0

Crystal structure of Danio rerio HDAC6 CD2 in complex with hydrolyzed DFMO-inhibitor (ITF7209)

spinqualitylabelsall models 9eu0, resolution 1.86Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9eu0 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 1.86Å Ligands: A1H7I, EPE, K, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function F8W4B7_DANRE Publication Abstract from PubMed 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. Mechanistic and Structural Insights on Difluoromethyl-1,3,4-oxadiazole Inhibitors of HDAC6.,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 Int J Mol Sci. 2024 May 28;25(11):5885. doi: 10.3390/ijms25115885. PMID:38892072 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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