9CTE

De novo design of protein catalysts for new-to-nature reactions

9CTE の概要

• エントリーDOI: 10.2210/pdb9cte/pdb
• 分子名称: De novo protein, 5,15-Diphenylporphyrin containing FE, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: metalloproteins, de novo protein
• 由来する生物種: synthetic construct
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 15816.35

構造登録者

Hou, K.,DeGrado, W.F. (登録日: 2024-07-25, 公開日: 2025-05-07, 最終更新日: 2025-05-21)

主引用文献

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

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: 40339022
DOI: 10.1126/science.adt7268

実験手法

X-RAY DIFFRACTION (2.26 Å)