Structure-based analysis of the effects of camptothecin on the activities of human topoisomerase I.

The sole target for the anticancer drug camptothecin (CPT) is the type I topoisomerase. The drug poisons the topoisomerase by slowing the religation step of the reaction, thereby trapping the enzyme in a covalent complex on the DNA. In addition, CPT has been shown to inhibit plasmid DNA relaxation in vitro. The structural bases for these two activities of CPT are explored in relation to the recently published crystal structure of the enzyme with bound DNA.