Journal: Cancer chemotherapy and pharmacology

Article Title: DNA Topoisomerase Targeting Chemotherapeutics: What’s New?

doi: 10.1007/s00280-017-3334-5

Figure Lengend Snippet: Type IB DNA topoisomerase. a) Human TOP1B (TOPO70) crystal structure with DNA and topotecan (TPT). Surface representation of the N-terminally truncated TOPO70 (lacking the first 174 residues) in orange with DNA (sticks) and TPT (blue balls), PDB# 1K4T [100]. All structure figures were generated using MacPyMol 0.99rc6 (DeLano Scientific, San Carlos, CA). b) Schematic representation of eukaryotic DNA topoisomerase I (TOP1B) catalytic cycle where the covalent enzyme-DNA intermediate constitutes the sole cellular target of camptothecin (CPT). Topotecan and irinotecan as FDA approved CPT analogs. TOP1B non-covalently circumscribes duplex DNA. The active side tyrosine cleaves one strand forming a 3’phospho-tyrosyl bond, which covalently links the enzyme to the 3’end of DNA. After DNA relaxation by a controlled rotation mechanism, the DNA ends religate and TOP1B may dissociate from the DNA. CPT intercalates into the cleavage site preventing religation of the DNA ends. The reversible drug-stabilized enzyme-DNA complex can be converted into lethal DNA lesions in collisions with processive replication or transcription machinery. See text for more details

Article Snippet: All structure figures were generated using MacPyMol 0.99rc6 (DeLano Scientific, San Carlos, CA). b) Schematic representation of eukaryotic DNA topoisomerase I (TOP1B) catalytic cycle where the covalent enzyme-DNA intermediate constitutes the sole cellular target of camptothecin (CPT).

Techniques: Generated