Asymmetric T-segment binding and gate dynamics govern the final stages of the type IIA topoisomerase catalytic cycle

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

Type IIA DNA topoisomerases are molecular nanomachines that alter DNA topology during essential cellular processes. The final steps of their catalytic cycle, after translocation of the transported (T-) segment into the C-gate, are still not fully understood. Here, we performed all-atom molecular dynamics simulations of several conformational states of Saccharomyces cerevisiae topoisomerase IIA, each with a T-segment inserted into the C-gate. Bound ATP and ADP nucleotides allosterically modulated the N-gate dynamics, likely stabilizing the dimer and preventing premature dissociation. The T-segment was asymmetrically bound and stabilized within the C-gate by positively charged residues, and this gate remained structurally rigid, highlighting its role as a retention site. The positioning of the T-segment in the C-gate allosterically influenced the G-segment to a straighter geometry that favors religation and release. Our simulations support coordinated release of DNA segments and point to a potentially important role for dynamic communication between the gates in the mechanism. These results provide new insights into the late stages of the catalytic cycle and highlight the intertwined roles of nucleotide binding, DNA topology and coupled protein domain dynamics in regulating this important enzyme.

• Jezik: Angleški jezik
• Ključne besede: type IIA DNA topoisomerase, T-segment, C-gate, catalytic cycle, 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: 2025
• Št. strani: 17 str.
• Številčenje: Vol. 327, pt. 1, art. 147216
• PID: 20.500.12556/RUL-182652
• UDK: 577
• ISSN pri članku: 1879-0003
• DOI: 10.1016/j.ijbiomac.2025.147216
• COBISS.SI-ID: 249271555
• Datum objave v RUL: 20.05.2026

Gradivo je del revije

• Naslov: International journal of biological macromolecules
• Skrajšan naslov: Int. j. biol. macromol.
• Založnik: Elsevier
• ISSN: 1879-0003
• COBISS.SI-ID: 23180805

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, topoizomeraza IIα, DNK, molekulska dinamika