9CTE
De novo design of protein catalysts for new-to-nature reactions
Summary for 9CTE
| Entry DOI | 10.2210/pdb9cte/pdb |
| Descriptor | De novo protein, 5,15-Diphenylporphyrin containing FE, CHLORIDE ION, ... (4 entities in total) |
| Functional Keywords | metalloproteins, de novo protein |
| Biological source | synthetic construct |
| Total number of polymer chains | 1 |
| Total formula weight | 15816.35 |
| Authors | Hou, K.,DeGrado, W.F. (deposition date: 2024-07-25, release date: 2025-05-07, Last modification date: 2025-05-21) |
| Primary citation | Hou, K.,Huang, W.,Qi, M.,Tugwell, T.H.,Alturaifi, T.M.,Chen, Y.,Zhang, X.,Lu, L.,Mann, S.I.,Liu, P.,Yang, Y.,DeGrado, W.F. De novo design of porphyrin-containing proteins as efficient and stereoselective catalysts. Science, 388:665-670, 2025 Cited by PubMed Abstract: De novo design of protein catalysts with high efficiency and stereoselectivity provides an attractive approach toward the design of environmentally benign catalysts. Here, we design proteins that incorporate histidine-ligated synthetic porphyrin and heme ligands. Four of 10 designed proteins catalyzed cyclopropanation with an enantiomeric ratio greater than 99:1. A second class of proteins were designed to catalyze a silicon-hydrogen insertion and were optimized by directed evolution in whole cells. The evolved proteins incorporated features unlikely to be generated by computational design alone, including a proline in an α helix. Molecular dynamics simulations showed that as the proteins evolved toward higher activity, their conformational ensembles narrowed to favor more productive conformations. Our work demonstrates that efficient de novo protein catalysts are designable and should be useful for manifold chemical processes. PubMed: 40339022DOI: 10.1126/science.adt7268 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.26 Å) |
Structure validation
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