6YQX
Crystal structure of DeNovoTIM13, a de novo designed TIM barrel
Summary for 6YQX
| Entry DOI | 10.2210/pdb6yqx/pdb |
| Descriptor | de novo designed TIM barrel DeNovoTIM13, GLYCEROL, CHLORIDE ION, ... (4 entities in total) |
| Functional Keywords | de novo protein design, epistasis, stability landscape, tim barrel, (beta/alfa)8 barrel, de novo protein |
| Biological source | synthetic construct |
| Total number of polymer chains | 1 |
| Total formula weight | 22245.23 |
| Authors | Romero-Romero, S.,Kordes, S.,Shanmugaratnam, S.,Fernandez-Velasco, D.A.,Hocker, B. (deposition date: 2020-04-18, release date: 2021-07-21, Last modification date: 2024-05-01) |
| Primary citation | Romero-Romero, S.,Costas, M.,Silva Manzano, D.A.,Kordes, S.,Rojas-Ortega, E.,Tapia, C.,Guerra, Y.,Shanmugaratnam, S.,Rodriguez-Romero, A.,Baker, D.,Hocker, B.,Fernandez-Velasco, D.A. The Stability Landscape of de novo TIM Barrels Explored by a Modular Design Approach. J.Mol.Biol., 433:167153-167153, 2021 Cited by PubMed Abstract: The ability to design stable proteins with custom-made functions is a major goal in biochemistry with practical relevance for our environment and society. Understanding and manipulating protein stability provide crucial information on the molecular determinants that modulate structure and stability, and expand the applications of de novo proteins. Since the (β/⍺)-barrel or TIM-barrel fold is one of the most common functional scaffolds, in this work we designed a collection of stable de novo TIM barrels (DeNovoTIMs), using a computational fixed-backbone and modular approach based on improved hydrophobic packing of sTIM11, the first validated de novo TIM barrel, and subjected them to a thorough folding analysis. DeNovoTIMs navigate a region of the stability landscape previously uncharted by natural TIM barrels, with variations spanning 60 degrees in melting temperature and 22 kcal per mol in conformational stability throughout the designs. Significant non-additive or epistatic effects were observed when stabilizing mutations from different regions of the barrel were combined. The molecular basis of epistasis in DeNovoTIMs appears to be related to the extension of the hydrophobic cores. This study is an important step towards the fine-tuned modulation of protein stability by design. PubMed: 34271011DOI: 10.1016/j.jmb.2021.167153 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.638 Å) |
Structure validation
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