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Schematic representation of TDP1 catalytic mechanism. Residue numbers refer to human TDP1. Curved arrows denote the transfer of electron pairs. (A) The imidazole N2 atom of H263 nucleophilically attacks the phosphate of the phosphotyrosyl group (B) Phosphohistidine covalent intermediate. (C) Hydrolysis of the phosphohistidine intermediate by H493-activated water molecule. (D) Generation of a final 3′ phosphate product and free TDP1.
