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

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

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.

• Jezik: Angleški jezik
• Ključne besede: type IIA DNA topoisomerase, T-segment, catalytic cycle, molecular simulations, molecular dynamics
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FFA - Fakulteta za farmacijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2024
• Št. strani: 17 str.
• Številčenje: Vol. 269, pt. 2, art. 131991
• PID: 20.500.12556/RUL-156341
• UDK: 577
• ISSN pri članku: 1879-0003
• DOI: 10.1016/j.ijbiomac.2024.131991
• COBISS.SI-ID: 195700995
• Datum objave v RUL: 21.05.2024

Gradivo je del revije

• Naslov: International journal of biological macromolecules
• Skrajšan naslov: Int. j. biol. macromol.
• Založnik: Elsevier
• ISSN: 1879-0003
• COBISS.SI-ID: 107163139

Licence

• Licenca: CC BY-NC-ND 4.0, Creative Commons Priznanje avtorstva-Nekomercialno-Brez predelav 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by-nc-nd/4.0/deed.sl
• Opis: Najbolj omejujoča licenca Creative Commons. Uporabniki lahko prenesejo in delijo delo v nekomercialne namene in ga ne smejo uporabiti za nobene druge namene.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: biokemija, topoizomeraze, DNK, encimi, simulacije