Structural highlights
Publication Abstract from PubMed
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 (beta/alpha)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.
De novo design of a four-fold symmetric TIM-barrel protein with atomic-level accuracy.,Huang PS, Feldmeier K, Parmeggiani F, Fernandez Velasco DA, Hocker B, Baker D Nat Chem Biol. 2015 Nov 23. doi: 10.1038/nchembio.1966. PMID:26595462[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Huang PS, Feldmeier K, Parmeggiani F, Fernandez Velasco DA, Hocker B, Baker D. De novo design of a four-fold symmetric TIM-barrel protein with atomic-level accuracy. Nat Chem Biol. 2015 Nov 23. doi: 10.1038/nchembio.1966. PMID:26595462 doi:http://dx.doi.org/10.1038/nchembio.1966
