Crystal structure of a covalently linked Aurora-A-MYCN complex
Please always quote using this URN: urn:nbn:de:bvb:20-opus-318855
- Formation of the Aurora-A–MYCN complex increases levels of the oncogenic transcription factor MYCN in neuroblastoma cells by abrogating its degradation through the ubiquitin proteasome system. While some small-molecule inhibitors of Aurora-A were shown to destabilize MYCN, clinical trials have not been satisfactory to date. MYCN itself is considered to be `undruggable' due to its large intrinsically disordered regions. Targeting the Aurora-A–MYCN complex rather than Aurora-A or MYCN alone will open new possibilities for drug development andFormation of the Aurora-A–MYCN complex increases levels of the oncogenic transcription factor MYCN in neuroblastoma cells by abrogating its degradation through the ubiquitin proteasome system. While some small-molecule inhibitors of Aurora-A were shown to destabilize MYCN, clinical trials have not been satisfactory to date. MYCN itself is considered to be `undruggable' due to its large intrinsically disordered regions. Targeting the Aurora-A–MYCN complex rather than Aurora-A or MYCN alone will open new possibilities for drug development and screening campaigns. To overcome the challenges that a ternary system composed of Aurora-A, MYCN and a small molecule entails, a covalently cross-linked construct of the Aurora-A–MYCN complex was designed, expressed and characterized, thus enabling screening and design campaigns to identify selective binders.…
Author: | Mathias Diebold, Lars Schönemann, Martin Eilers, Christoph Sotriffer, Hermann Schindelin |
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URN: | urn:nbn:de:bvb:20-opus-318855 |
Document Type: | Journal article |
Faculties: | Fakultät für Biologie / Theodor-Boveri-Institut für Biowissenschaften |
Fakultät für Biologie / Rudolf-Virchow-Zentrum | |
Fakultät für Chemie und Pharmazie / Institut für Pharmazie und Lebensmittelchemie | |
Language: | English |
Parent Title (English): | Acta Crystallographica |
Year of Completion: | 2023 |
Volume: | D79 |
First Page: | 1 |
Last Page: | 9 |
Source: | Acta Crystallographica 2023, D79:1-9. DOI: 10.1107/s2059798322011433 |
DOI: | https://doi.org/10.1107/s2059798322011433 |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Tag: | MYCNv; neuroblastoma cell; proteasome system |
Release Date: | 2023/08/11 |
Licence (German): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |