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De novo design of a four-fold symmetric TIM-barrel protein with atomic-level accuracy

Title data

Huang, Po-Ssu ; Feldmeier, Kaspar ; Parmeggiani, Fabio ; Velasco, D Alejandro Fernandez ; Höcker, Birte ; Baker, David:
De novo design of a four-fold symmetric TIM-barrel protein with atomic-level accuracy.
In: Nature Chemical Biology. Vol. 12 (January 2016) Issue 1 . - pp. 29-34.
ISSN 1552-4469
DOI: https://doi.org/10.1038/nchembio.1966

Project information

Project financing: Deutsche Forschungsgemeinschaft
IMPRS fellowship

Abstract in another language

Despite efforts for over 25 years, de novo protein design has not succeeded in achieving the TIM-barrel fold. Here we describe the computational design of four-fold symmetrical (β/α)8 barrels guided by geometrical and chemical principles. Experimental characterization of 33 designs revealed the importance of side chain-backbone hydrogen bonds for defining the strand register between repeat units. The X-ray crystal structure of a designed thermostable 184-residue protein is nearly identical to that of the designed TIM-barrel model. PSI-BLAST searches do not identify sequence similarities to known TIM-barrel proteins, and sensitive profile-profile searches indicate that the design sequence is distant from other naturally occurring TIM-barrel superfamilies, suggesting that Nature has sampled only a subset of the sequence space available to the TIM-barrel fold. The ability to design TIM barrels de novo opens new possibilities for custom-made enzymes.

Further data

Item Type: Article in a journal
Refereed: Yes
Institutions of the University: Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Chair Biochemistry > Chair Biochemistry - Univ.-Prof. Dr. Birte Höcker
Result of work at the UBT: No
DDC Subjects: 500 Science > 540 Chemistry
500 Science > 570 Life sciences, biology
Date Deposited: 13 May 2019 09:25
Last Modified: 13 May 2019 09:25
URI: https://eref.uni-bayreuth.de/id/eprint/48921