Figure 3.

Gate padlocks can regulate topoisomerase activity and clamp interacting DNA. Analogously to bisdioxopiperazines, such as ICRF-193 that inhibit topoisomerase II activity, closure of the N-gate of topoisomerase II upon ATP binding can be stabilized also by some cellular factor. (A) Such gate padlocks could operate as inhibitors of enzyme binding to chromosomal DNA. (B) If DNA is already bound to the topoisomerase, an N-gate padlock would produce a high salt resistant complex, which might serve to regulate the enzyme activity or operate as a structural element for DNA organization. (C) Padlocks for the C-gate could also exist. If both the N-gate and the C-gate were stabilized in the closed conformation, the topoisomerase could clamp two DNA duplexes, the G-segment and passed T-segment.