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Int. J. Mol. Sci. 2018, 19(4), 1133;

Allosteric Activation of GDP-Bound Ras Isoforms by Bisphenol Derivative Plasticisers

Faculty of Chemistry and Biochemistry, Ruhr University of Bochum, Universitätsstr. 150, D-44780 Bochum, Germany
Skin Cancer Unit of the Dermatology Department, West German Cancer Center, University Hospital Essen, University Duisburg-Essen and the German Cancer Consortium (DKTK), D-45147 Essen, Germany
Institute of Pharmacology and Toxicology, Witten/Herdecke University, Stockumer Str. 10, D-58453 Witten, Germany
Faculty of Mathematics and Natural Sciences, University of Wuppertal, Gaußstr. 20, D-42119 Wuppertal, Germany
Author to whom correspondence should be addressed.
Received: 27 February 2018 / Revised: 4 April 2018 / Accepted: 5 April 2018 / Published: 10 April 2018
(This article belongs to the Special Issue Advances in the Research of Endocrine Disrupting Chemicals)
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The protein family of small GTPases controls cellular processes by acting as a binary switch between an active and an inactive state. The most prominent family members are H-Ras, N-Ras, and K-Ras isoforms, which are highly related and frequently mutated in cancer. Bisphenols are widespread in modern life because of their industrial application as plasticisers. Bisphenol A (BPA) is the best-known member and has gained significant scientific as well as public attention as an endocrine disrupting chemical, a fact that eventually led to its replacement. However, compounds used to replace BPA still contain the molecular scaffold of bisphenols. BPA, BPAF, BPB, BPE, BPF, and an amine-substituted BPAF-derivate all interact with all GDP-bound Ras-Isoforms through binding to a common site on these proteins. NMR-, SOScat-, and GDI- assay-based data revealed a new bisphenol-induced, allosterically activated GDP-bound Ras conformation that define these plasticisers as Ras allosteric agonists. View Full-Text
Keywords: bisphenols; K-Ras4B; Rap-1A; NMR spectroscopy; active conformation/allosteric agonists bisphenols; K-Ras4B; Rap-1A; NMR spectroscopy; active conformation/allosteric agonists

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Schöpel, M.; Shkura, O.; Seidel, J.; Kock, K.; Zhong, X.; Löffek, S.; Helfrich, I.; Bachmann, H.S.; Scherkenbeck, J.; Herrmann, C.; Stoll, R. Allosteric Activation of GDP-Bound Ras Isoforms by Bisphenol Derivative Plasticisers. Int. J. Mol. Sci. 2018, 19, 1133.

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