9MRB

The designed serine hydrolase known as dad_t1

9MRB の概要

• エントリーDOI: 10.2210/pdb9mrb/pdb
• 分子名称: dad_t1, TETRAETHYLENE GLYCOL (3 entities in total)
• 機能のキーワード: enzyme, serine hydrolase, 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: 18133.47

構造登録者

Pellock, S.J.,Lauko, A.,Bera, A.,Baker, D. (登録日: 2025-01-07, 公開日: 2025-02-19, 最終更新日: 2025-04-30)

主引用文献

Lauko, A.,Pellock, S.J.,Sumida, K.H.,Anishchenko, I.,Juergens, D.,Ahern, W.,Jeung, J.,Shida, A.F.,Hunt, A.,Kalvet, I.,Norn, C.,Humphreys, I.R.,Jamieson, C.,Krishna, R.,Kipnis, Y.,Kang, A.,Brackenbrough, E.,Bera, A.K.,Sankaran, B.,Houk, K.N.,Baker, D.
Computational design of serine hydrolases.
Science, 388:eadu2454-eadu2454, 2025

PubMed Abstract: The design of enzymes with complex active sites that mediate multistep reactions remains an outstanding challenge. With serine hydrolases as a model system, we combined the generative capabilities of RFdiffusion with an ensemble generation method for assessing active site preorganization at each step in the reaction to design enzymes starting from minimal active site descriptions. Experimental characterization revealed catalytic efficiencies (/) up to 2.2 × 10 M s and crystal structures that closely match the design models (Cα root mean square deviations <1 angstrom). Selection for structural compatibility across the reaction coordinate enabled identification of new catalysts remove with five different folds distinct from those of natural serine hydrolases. Our de novo approach provides insight into the geometric basis of catalysis and a roadmap for designing enzymes that catalyze multistep transformations.

PubMed: 39946508
DOI: 10.1126/science.adu2454

実験手法

X-RAY DIFFRACTION (2 Å)