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URN to cite this document: urn:nbn:de:bvb:703-epub-7964-6
Title data
Beck, Julian ; Shanmugaratnam, Sooruban ; Höcker, Birte:
Diversifying de novo TIM barrels by hallucination.
In: Protein Science.
Vol. 33
(2024)
Issue 6
.
- e5001.
ISSN 1469-896X
DOI der Verlagsversion: https://doi.org/10.1002/pro.5001
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Abstract
De novo protein design expands the protein universe by creating new sequences to accomplish tailor-made enzymes in the future. A promising topology to implement diverse enzyme functions is the ubiquitous TIM-barrel fold. Since the initial de novo design of an idealized four-fold symmetric TIM barrel, the family of de novo TIM barrels is expanding rapidly. Despite this and in contrast to natural TIM barrels, these novel proteins lack cavities and structural elements essential for the incorporation of binding sites or enzymatic functions. In this work, we diversified a de novo TIM barrel by extending multiple βα-loops using constrained hallucination. Experimentally tested designs were found to be soluble upon expression in Escherichia coli and well-behaved. Biochemical characterization and crystal structures revealed successful extensions with defined α-helical structures. These diversified de novo TIM barrels provide a framework to explore a broad spectrum of functions based on the potential of natural TIM barrels.
Further data
| Item Type: | Article in a journal |
|---|---|
| Keywords: | (βα)8‐barrel; de novo protein design; hallucination; machine learning; small molecule binding site |
| DDC Subjects: | 500 Science > 500 Natural sciences 500 Science > 540 Chemistry 500 Science > 570 Life sciences, biology |
| Institutions of the University: | Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Chair Biochemistry III - Protein Design > Chair Biochemistry III - Protein Design - Univ.-Prof. Dr. Birte Höcker Faculties Faculties > Faculty of Biology, Chemistry and Earth Sciences Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Chair Biochemistry III - Protein Design |
| Language: | English |
| Originates at UBT: | Yes |
| URN: | urn:nbn:de:bvb:703-epub-7964-6 |
| Date Deposited: | 07 Oct 2024 05:58 |
| Last Modified: | 07 Oct 2024 05:58 |
| URI: | https://epub.uni-bayreuth.de/id/eprint/7964 |
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