Allosteric activation of GDP-bound ras isoforms by bisphenol derivative plasticisers
- 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-, \(SOS^{cat_{-}}\), and GDI- assay-based data revealed a new bisphenol-induced, allosterically activated GDP-bound Ras conformation that define these plasticisers as Ras allosteric agonists.
| Author: | Miriam SchöpelGND, Oleksandr ShkuraGND, Jana SeidelGND, Klaus KockGND, Xueyin ZhongGND, Stefanie LöffekGND, Iris HelfrichGND, Hagen S. BachmannGND, Jürgen ScherkenbeckGND, Christian HerrmannORCiDGND, Raphael StollORCiDGND |
|---|---|
| URN: | urn:nbn:de:hbz:294-60100 |
| DOI: | https://doi.org/10.3390/ijms19041133 |
| Parent Title (English): | International journal of molecular sciences |
| Document Type: | Article |
| Language: | English |
| Date of Publication (online): | 2018/07/20 |
| Date of first Publication: | 2018/04/10 |
| Publishing Institution: | Ruhr-Universität Bochum, Universitätsbibliothek |
| Tag: | Open Access Fonds K-Ras4B; NMR spectroscopy; Rap-1A; active conformation/allosteric agonists; bisphenols |
| Volume: | 19 |
| Issue: | 4 |
| First Page: | 1 |
| Last Page: | 14 |
| Note: | Article Processing Charge funded by the Deutsche Forschungsgemeinschaft (DFG) and the Open Access Publication Fund of Ruhr-Universität Bochum. |
| Dewey Decimal Classification: | Naturwissenschaften und Mathematik / Biowissenschaften, Biologie, Biochemie |
| open_access (DINI-Set): | open_access |
| faculties: | Fakultät für Chemie und Biochemie |
| Licence (English): |  Creative Commons - CC BY 4.0 - Attribution 4.0 International |
