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Molecular choreography : unveiling the dynamic landscape of type IIA DNA topoisomerases before T-segment passage through all-atom simulations
ID
Herlah, Barbara
(
Author
),
ID
Pavlin, Matic
(
Author
),
ID
Perdih, Andrej
(
Author
)
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https://www.sciencedirect.com/science/article/pii/S014181302402796X
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Abstract
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
Views:
194
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41
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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
Projects
Funder:
ARIS - Slovenian Research and Innovation Agency
Project number:
J1-4402
Name:
Dinamični model molekulskega stroja DNA topoizomeraze tipa II in razvoj katalitičnih inhibitorjev
Funder:
ARIS - Slovenian Research and Innovation Agency
Project number:
P1-0012
Name:
Molekulske simulacije, bioinformatika in načrtovanje zdravilnih učinkovin
Funder:
ARIS - Slovenian Research and Innovation Agency
Project number:
P2-0152
Name:
Kemijsko reakcijsko inženirstvo
Funder:
ARIS - Slovenian Research and Innovation Agency
Funding programme:
Young researchers
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