Conformational Changes and ATP Hydrolysis in Zika Helicase. The Molecular Basis of a Biomolecular Motor Unveiled by Multiscale Simulations
We computationally study Zika NS3 helicase, a biological motor using ATP hydrolysis energy for nucleic acid remodelling. Through classical and QM/MM simulations, we explore the conformational landscape of Motif V, a conserved loop connecting the active sites for ATP hydrolysis and nucleic acid binding. ATP hydrolysis, initiated by a meta-phosphate group formation, involves the nucleophilic attack of a water molecule activated by Glu286 proton abstraction. Motif V hydrogen bonds to this water via Gly415 backbone NH group, assisting hydrolysis. Post-hydrolysis, free energy is released when the inorganic phosphate moves away from the coordination shell of the magnesium ion, inducing a significant shift in the conformational landscape of Motif V to establish a hydrogen bond between Gly415 NH and Glu285. Zika NS3 helicase acts as a ratchet biological motor with Motif V transitions steered by Gly415’s γ-phosphate sensing in the ATPase site..
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Preprint| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
chemRxiv.org - (2023) vom: 02. Aug. Zur Gesamtaufnahme - year:2023 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
García-Martínez, Adrián [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.26434/chemrxiv-2023-5krqd |
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XCH040403319 |
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| 100 | 1 | |a García-Martínez, Adrián |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Conformational Changes and ATP Hydrolysis in Zika Helicase. The Molecular Basis of a Biomolecular Motor Unveiled by Multiscale Simulations |
| 264 | 1 | |c 2023 | |
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| 520 | |a We computationally study Zika NS3 helicase, a biological motor using ATP hydrolysis energy for nucleic acid remodelling. Through classical and QM/MM simulations, we explore the conformational landscape of Motif V, a conserved loop connecting the active sites for ATP hydrolysis and nucleic acid binding. ATP hydrolysis, initiated by a meta-phosphate group formation, involves the nucleophilic attack of a water molecule activated by Glu286 proton abstraction. Motif V hydrogen bonds to this water via Gly415 backbone NH group, assisting hydrolysis. Post-hydrolysis, free energy is released when the inorganic phosphate moves away from the coordination shell of the magnesium ion, inducing a significant shift in the conformational landscape of Motif V to establish a hydrogen bond between Gly415 NH and Glu285. Zika NS3 helicase acts as a ratchet biological motor with Motif V transitions steered by Gly415’s γ-phosphate sensing in the ATPase site. | ||
| 650 | 4 | |a Chemistry |7 (dpeaa)DE-84 | |
| 650 | 4 | |a 540 |7 (dpeaa)DE-84 | |
| 700 | 1 | |a Zinovjev, Kirill |4 aut | |
| 700 | 1 | |a Ruiz-Pernía, J. Javier |4 aut | |
| 700 | 1 | |a Tuñón, Iñaki |0 (orcid)0000-0002-6995-1838 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t chemRxiv.org |g (2023) vom: 02. Aug. |
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