Article by this assay is an IC50 of ∼1 μM because the JMJD2E enzyme concentration required to achieve sufficient sensitivity in the current assay conditions is 2 μM. Statistical analyses on correlation between MS and % inhibi- tion rankings were carried out using Kendall’s τB and Spearman’s rank correlation tests, using StatsDirect, http://www.statsdirect. com. Crystals of JMJD2A:10a were grown by vapor diffusion at 4 C in 200 nL sitting drops, with a 1:1 protein to reservoir solution ratio. The JMJD2A protein solution for crystalliza- tion was composed of 11.0 mg/mL protein, 10 mM HEPES pH 7.5, 500 mM NaCl, 5% v/v glycerol, and 0.75 mM 10a. The reservoir solution included 0.1 M citrate pH 5.5, 18.5% w/v polyethylene glycol 3350, 4 mM NiCl2. The crystals were cryo- protected by transferring to 25% v/v glycerol in well solution and flash frozen by rapidly plunging in liquid nitrogen. Data were collected from a single crystal at 100 K at the Diamond Light Source beamline I03 using 0.97860 A˚ wavelength beam. The data were processed with MOSFLM and SCALA.36 Iterative rounds of model building in COOT37 and refinement using REFMAC36 resulted in the final model with R = 18.1% and Rfree = 24.8%. All residues were in acceptable regions of a Ramachandran plot as calculated by MolProbity.38 Refinement details are shown in Table S2 of the Supporting Information. Acknowledgment. This work was supported by the Com- monwealth Scholarship Commission (N.R.), the Newton- Abraham Fund (J.M.), the Biotechnology and Biological Sciences Research Council, Cancer Research UK (G.K.), the Wellcome Trust, and the European Union, The Structural Genomics Consortium is a registered charity (no. 1097737) that receives funds from multiple sources, details of which are found in the Supporting Information. The project was supported by the Oxford NIHR Musculoskeletal Biomedical Research Unit. 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