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. Author manuscript; available in PMC: 2015 Jul 1.
Published in final edited form as: DNA Repair (Amst). 2014 May 22;19:114–129. doi: 10.1016/j.dnarep.2014.03.020

Fig. 5.

Fig. 5

TDP1 catalytic cycle. (A) Nucleophilic attack of the phosphodiester backbone by the imidazole N2 atom of H263. H493 donates a proton to the tyrosyl moiety of the leaving group. (B) Phosphohistidine covalent intermediate. (C) Second nucleophilic attack via an activated water molecule by H493. (D): Generation of a final 3′-phosphate product and free TDP1. (E) The SCAN-1 mutations (H493R) leads to an accumulation of the Tdp1-DNA intermediate and a defect in TDP1 turn- over rate.