Fig. 7.
Proposed reaction mechanism for phosphodiester bond cleavage by TDP2. (A) Top2-derived peptide (trapped topoisomerase) linked to 5′-DNA via a phosphotyrosyl bond. (B) Upon binding of the covalent peptide-DNA substrate in the Tdp2 active site, two magnesium ions are coordinated by the TDP2 catalytic residues for nucleophilic attack of the phosphotyrosyl bond (black arrows) [134]. (C) Cleavage products consisting in the topoisomerase polypeptide (top) and the liberated DNA with a 5′-phosphate end.