9QDP

De novo designed enzyme for Morita-Baylis-Hillman reaction MBH2

9QDP の概要

• エントリーDOI: 10.2210/pdb9qdp/pdb
• 分子名称: De novo designed enzyme for Morita-Baylis-Hillman reaction MBH2, TRIETHYLENE GLYCOL, SODIUM ION, ... (4 entities in total)
• 機能のキーワード: morita-baylis-hillman enzyme, 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: 23463.96

構造登録者

Tripp, A.,Stoll, D.,Oberdorfer, G.,Fischer, C.,Kaltenbrunner, S. (登録日: 2025-03-06, 公開日: 2025-12-10, 最終更新日: 2026-01-07)

主引用文献

Braun, M.,Tripp, A.,Chakatok, M.,Kaltenbrunner, S.,Fischer, C.,Stoll, D.,Bijelic, A.,Elaily, W.,Totaro, M.G.,Moser, M.,Hoch, S.Y.,Lechner, H.,Rossi, F.,Aleotti, M.,Hall, M.,Oberdorfer, G.
Computational enzyme design by catalytic motif scaffolding.
Nature, 649:237-245, 2026

PubMed Abstract: Enzymes find broad use as biocatalysts in industry and medicine owing to their exquisite selectivity, efficiency and mild reaction conditions. Custom-designed enzymes can produce tailor-made biocatalysts with potential applications that extend beyond natural reactions. However, current design methods require testing a large number of designs and mostly produce de novo enzymes with low catalytic activities. As a result, they require costly experimental optimization and high-throughput screening to be industrially viable. Here we present rotamer inverted fragment finder-diffusion (Riff-Diff), a hybrid machine learning and atomistic modelling strategy for scaffolding catalytic arrays in de novo proteins. We highlight the general applicability of Riff-Diff by designing enzymes for two mechanistically distinct chemical transformations, the retro-aldol reaction and the Morita-Baylis-Hillman reaction. We show that in both cases, it is possible to generate catalysts that exhibit activities rivalling those optimized by in vitro evolution, along with exquisite stereoselectivity. High-resolution structures of six of the designs revealed near-atomic active site design precision. The design strategy can, in principle, be applied to any catalytically competent amino acid array. These findings lay the basis for practical applicability of de novo protein catalysts in synthesis and describe fundamental principles of protein design and enzyme catalysis.

PubMed: 41339546
DOI: 10.1038/s41586-025-09747-9

実験手法

X-RAY DIFFRACTION (1.17 Å)