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The initial |Fo|–|Fc| map (two orientations (A) and (B)) calculated from X-ray diffraction data collected from crystals of HDAC6 cocrystallized with inhibitor 6 reveals strong, unbiased electron density for the bound inhibitor in the active site. Surprisingly, this difference density could not be fit satisfactorily with intact oxadiazole 6 (C); instead, it could be fit perfectly with acylhydrazide 13 resulting from hydrolysis and ring-opening of the oxadiazole (D).
