Conformational Changes and ATP Hydrolysis in Zika Helicase : The Molecular Basis of a Biomolecular Motor Unveiled by Multiscale Simulations
We computationally study the Zika NS3 helicase, a biological motor, using ATP hydrolysis energy for nucleic acid remodeling. Through molecular mechanics and hybrid quantum mechanics/molecular mechanics 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 the Gly415 backbone NH group, assisting hydrolysis. Posthydrolysis, 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 the Gly415 NH group and Glu285. According to our simulations, the Zika NS3 helicase acts as a ratchet biological motor with motif V transitions steered by Gly415's γ-phosphate sensing in the ATPase site.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:145 |
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| Enthalten in: |
Journal of the American Chemical Society - 145(2023), 45 vom: 15. Nov., Seite 24809-24819 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
García-Martínez, Adrián [VerfasserIn] |
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| Links: |
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| Themen: |
059QF0KO0R |
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| Anmerkungen: |
Date Completed 14.02.2024 Date Revised 14.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1021/jacs.3c09015 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM364134461 |
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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 |b The Molecular Basis of a Biomolecular Motor Unveiled by Multiscale Simulations |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Completed 14.02.2024 | ||
| 500 | |a Date Revised 14.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a We computationally study the Zika NS3 helicase, a biological motor, using ATP hydrolysis energy for nucleic acid remodeling. Through molecular mechanics and hybrid quantum mechanics/molecular mechanics 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 the Gly415 backbone NH group, assisting hydrolysis. Posthydrolysis, 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 the Gly415 NH group and Glu285. According to our simulations, the 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 Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Adenosine Triphosphate |2 NLM | |
| 650 | 7 | |a 8L70Q75FXE |2 NLM | |
| 650 | 7 | |a DNA Helicases |2 NLM | |
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| 650 | 7 | |a Water |2 NLM | |
| 650 | 7 | |a 059QF0KO0R |2 NLM | |
| 650 | 7 | |a Phosphates |2 NLM | |
| 700 | 1 | |a Zinovjev, Kirill |e verfasserin |4 aut | |
| 700 | 1 | |a Ruiz-Pernía, José Javier |e verfasserin |4 aut | |
| 700 | 1 | |a Tuñón, Iñaki |e verfasserin |4 aut | |
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