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20 results on '"Tőke, Orsolya"'

8. The Importance of Mg2+‐Free State in Nucleotide Exchange of Oncogenic K‐Ras Mutants.

Author

Pálfy, Gyula, Menyhárd, Dóra K., Ákontz‐Kiss, Hanna, Vida, István, Batta, Gyula, Tőke, Orsolya, and Perczel, András

Subjects
RAS proteins, NUCLEOTIDE exchange factors, MOLECULAR dynamics, RELAXATION techniques
Abstract

For efficient targeting of oncogenic K‐Ras interaction sites, a mechanistic picture of the Ras‐cycle is necessary. Herein, we used NMR relaxation techniques and molecular dynamics simulations to decipher the role of slow dynamics in wild‐type and three oncogenic P‐loop mutants of K‐Ras. Our measurements reveal a dominant two‐state conformational exchange on the ms timescale in both GDP‐ and GTP‐bound K‐Ras. The identified low‐populated higher energy state in GDP‐loaded K‐Ras has a conformation reminiscent of a nucleotide‐bound/Mg2+‐free state characterized by shortened β2/β3‐strands and a partially released switch‐I region preparing K‐Ras for the interaction with the incoming nucleotide exchange factor and subsequent reactivation. By providing insight into mutation‐specific differences in K‐Ras structural dynamics, our systematic analysis improves our understanding of prolonged K‐Ras signaling and may aid the development of allosteric inhibitors targeting nucleotide exchange in K‐Ras. [ABSTRACT FROM AUTHOR]

Published
2022
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12. Structural insights into the tyrosine phosphorylation–mediated inhibition of SH3 domain–ligand interactions

Author

Merő, Balázs, primary, Radnai, László, additional, Gógl, Gergő, additional, Tőke, Orsolya, additional, Leveles, Ibolya, additional, Koprivanacz, Kitti, additional, Szeder, Bálint, additional, Dülk, Metta, additional, Kudlik, Gyöngyi, additional, Vas, Virág, additional, Cserkaszky, Anna, additional, Sipeki, Szabolcs, additional, Nyitray, László, additional, Vértessy, Beáta G., additional, and Buday, László, additional

Published
2019
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13. The SH3 domain of Caskin1 binds to lysophosphatidic acid suggesting a direct role for the lipid in intracellular signaling

Author

Koprivanacz, Kitti, primary, Tőke, Orsolya, additional, Besztercei, Balázs, additional, Juhász, Tünde, additional, Radnai, László, additional, Merő, Balázs, additional, Mihály, Judith, additional, Péter, Mária, additional, Balogh, Gábor, additional, Vígh, László, additional, Buday, László, additional, and Liliom, Károly, additional

Published
2017
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18. Glutamate Uptake Triggers Transporter-Mediated GABA Release from Astrocytes

Author

Héja, László, primary, Barabás, Péter, additional, Nyitrai, Gabriella, additional, Kékesi, Katalin A., additional, Lasztóczi, Bálint, additional, Tőke, Orsolya, additional, Tárkányi, Gábor, additional, Madsen, Karsten, additional, Schousboe, Arne, additional, Dobolyi, Árpád, additional, Palkovits, Miklós, additional, and Kardos, Julianna, additional

Published
2009
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20. The Importance of Mg 2+ -Free State in Nucleotide Exchange of Oncogenic K-Ras Mutants.

Author

Pálfy G, Menyhárd DK, Ákontz-Kiss H, Vida I, Batta G, Tőke O, and Perczel A

Subjects
Mutation, Guanosine Triphosphate chemistry, Nucleotides, Molecular Dynamics Simulation
Abstract

For efficient targeting of oncogenic K-Ras interaction sites, a mechanistic picture of the Ras-cycle is necessary. Herein, we used NMR relaxation techniques and molecular dynamics simulations to decipher the role of slow dynamics in wild-type and three oncogenic P-loop mutants of K-Ras. Our measurements reveal a dominant two-state conformational exchange on the ms timescale in both GDP- and GTP-bound K-Ras. The identified low-populated higher energy state in GDP-loaded K-Ras has a conformation reminiscent of a nucleotide-bound/Mg 2+ -free state characterized by shortened β2/β3-strands and a partially released switch-I region preparing K-Ras for the interaction with the incoming nucleotide exchange factor and subsequent reactivation. By providing insight into mutation-specific differences in K-Ras structural dynamics, our systematic analysis improves our understanding of prolonged K-Ras signaling and may aid the development of allosteric inhibitors targeting nucleotide exchange in K-Ras., (© 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Published
2022
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