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Kordes, Sina ; Beck, Julian ; Shanmugaratnam, Sooruban ; Flecks, Merle ; Höcker, Birte:
Physics-based approach to extend a de novo TIM barrel with rationally designed helix-loop-helix motifs.
In: Protein Engineering, Design & Selection.
Bd. 36
(2023)
.
- gzad012.
ISSN 1741-0134
DOI: https://doi.org/10.1093/protein/gzad012
Abstract
Computational protein design promises the ability to build tailor-made proteins de novo. While a range of de novo proteins have been constructed so far, the majority of these designs have idealized topologies that lack larger cavities which are necessary for the incorporation of small molecule binding sites or enzymatic functions. One attractive target for enzyme design is the TIM-barrel fold, due to its ubiquity in nature and capability to host versatile functions. With the successful de novo design of a 4-fold symmetric TIM barrel, sTIM11, an idealized, minimalistic scaffold was created. In this work, we attempted to extend this de novo TIM barrel by incorporating a helix-loop-helix motif into its βα-loops by applying a physics-based modular design approach using Rosetta. Further diversification was performed by exploiting the symmetry of the scaffold to integrate two helix-loop-helix motifs into the scaffold. Analysis with AlphaFold2 and biochemical characterization demonstrate the formation of additional α-helical secondary structure elements supporting the successful extension as intended.
Weitere Angaben
| Publikationsform: | Artikel in einer Zeitschrift |
|---|---|
| Begutachteter Beitrag: | Ja |
| Keywords: | (βα)8-barrel; TIM-barrel; computational protein design; helix-loop-helix |
| Institutionen der Universität: | Fakultäten > Fakultät für Biologie, Chemie und Geowissenschaften > Fachgruppe Chemie > Lehrstuhl Biochemie > Lehrstuhl Biochemie III - Proteindesign - Univ.-Prof. Dr. Birte Höcker |
| Titel an der UBT entstanden: | Ja |
| Themengebiete aus DDC: | 500 Naturwissenschaften und Mathematik > 540 Chemie |
| Eingestellt am: | 14 Nov 2023 08:17 |
| Letzte Änderung: | 14 Nov 2023 10:30 |
| URI: | https://eref.uni-bayreuth.de/id/eprint/87724 |