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Custom Vector Construction> | … The pCDNA3.1 vector containing the full-length (1–3056) human ATM gene was ordered from GenScript. Human ATM was designed to comprise an N-terminal FLAG tag (MDYKDDDDK) and codons optimized for protein expression in mammalian cells. … | Get A Quote |
Human checkpoint kinase ataxia telangiectasia-mutated (ATM) plays a key role in initiation of the DNA damage response following DNA double-strand breaks. ATM inhibition is a promising approach in cancer therapy, but, so far, detailed insights into the binding modes of known ATM inhibitors have been hampered due to the lack of high-resolution ATM structures. Using cryo-EM, we have determined the structure of human ATM to an overall resolution sufficient to build a near-complete atomic model and identify two hitherto unknown zinc-binding motifs. We determined the structure of the kinase domain bound to ATPγS and to the ATM inhibitors KU-55933 and M4076 at 2.8 Å, 2.8 Å and 3.0 Å resolution, respectively.... More