Figure 5.

Catalytic cycle of TDP2. (A) Active site of TDP2 accommodates the 5′-phosphotyrosyl–DNA adduct. (B) Nucleophilic water is activated by D272. ‘O–P’ bond formed between the water ‘O’ and DNA ‘P’ forming the penta-covalent intermediate. Mg²⁺ ion represented as a yellow sphere stabilizes the 5′-phosphate of the DNA. (C) Breakage of the phosphotyrosyl bond causes the release of the Top II peptide and DNA 5′-phosphate.