20.500.12556/RUL-156341 Molecular choreography unveiling the dynamic landscape of type IIA DNA topoisomerases before T-segment passage through all-atom simulations Type IIA DNA topoisomerases are molecular nanomachines responsible for controlling topological states of DNA molecules. Here, we explore the dynamic landscape of yeast topoisomerase IIA during key stages of its catalytic cycle, focusing in particular on the events preceding the passage of the T-segment. To this end, we generated six configurations of fully catalytic yeast topo IIA, strategically inserted a T-segment into the N-gate in relevant configurations, and performed all-atom simulations. The essential motion of topo IIA protein dimer was characterized by rotational gyrating-like movement together with sliding motion within the DNA-gate. Both appear to be inherent properties of the enzyme and an inbuilt feature that allows passage of the T-segment through the cleaved G-segment. Coupled dynamics of the Ngate and DNA-gate residues may be particularly important for controlled and smooth passage of the T-segment and consequently the prevention of DNA double-strand breaks. QTK loop residue Lys367, which interacts with ATP and ADP molecules, is involved in regulating the size and stability of the N-gate. The unveiled features of the simulated configurations provide insights into the catalytic cycle of type IIA topoisomerases and elucidate the molecular choreography governing their ability to modulate the topological states of DNA topology. type IIA DNA topoisomerase T-segment catalytic cycle molecular simulations molecular dynamics biokemija topoizomeraze DNK encimi simulacije true false true Angleški jezik Slovenski jezik Članek v reviji 2024-05-21 09:11:10 2024-05-21 09:11:11 2024-05-22 03:48:13 0000-00-00 00:00:00 2024 0 0 17 str. pt. 2, art. 131991 Vol. 269 Jun. 2024 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 577 1879-0003 10.1016/j.ijbiomac.2024.131991 195700995 1-s2.0-S014181302402796X-main.pdf 1-s2.0-S014181302402796X-main.pdf 1 D12768BFE83CF5E3689934CD54064388 6c855ad1ac2246d69c859e2f789c6f1ac582c8887dd7a53e0b99a21e5b6a1b44 a2b30d70-1741-11ef-b8e5-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=183752 https://www.sciencedirect.com/science/article/pii/S014181302402796X 1 4e025299-1741-11ef-b8e5-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=183751 Fakulteta za farmacijo 0 0 0