Fig. 2. X-ray crystallography and protein-observed SPE-MS studies inform on the mechanism of DEK inhibition. (A) Views from a crystal structure derived by reaction of LdtMt2 with DEK 1 (yellow, PDB: 8BK3). The immunoglobulin-like domains are in teal and cyan. The catalytic domain is grey, with the active site lid in green. The mFo-DFc polder OMIT map is contoured at 3.0σ, carved around Cys354 bound 1 (refined as 3) and shown in blue mesh. Polar interactions are shown in black dashes. (B) Protein-observed SPE-MS experiments inform on the mechanism of reaction of 1 (20 μM) with LdtMt2 (1 μM). (C) The proposed mechanisms for reaction of Cys354 of LdtMt2 (in green) with 1via reaction with (i) the carbonyl adjacent carbon or (ii) the carbonyl carbon, followed by retro-aldol fragmentation.
