Molecular choreography : unveiling the dynamic landscape of type IIA DNA topoisomerases before T-segment passage through all-atom simulations

Herlah, Barbara (author), Pavlin, Matic (author), Perdih, Andrej (author)

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.

• Language: English
• Keywords: type IIA DNA topoisomerase, T-segment, catalytic cycle, molecular simulations, molecular dynamics
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2024
• Number of pages: 17 str.
• Numbering: Vol. 269, pt. 2, art. 131991
• PID: 20.500.12556/RUL-156341
• UDC: 577
• ISSN on article: 1879-0003
• DOI: 10.1016/j.ijbiomac.2024.131991
• COBISS.SI-ID: 195700995
• Publication date in RUL: 21.05.2024

Record is a part of a journal

• Title: International journal of biological macromolecules
• Shortened title: Int. j. biol. macromol.
• Publisher: Elsevier
• ISSN: 1879-0003
• COBISS.SI-ID: 107163139

Licences

• License: CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
• Link: http://creativecommons.org/licenses/by-nc-nd/4.0/
• Description: The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.

Secondary language

• Language: Slovenian
• Keywords: biokemija, topoizomeraze, DNK, encimi, simulacije