8P5Y

Artificial transfer hydrogenase with a Mn-12 cofactor and Streptavidin S112Y-K121M mutant

8P5Y の概要

• エントリーDOI: 10.2210/pdb8p5y/pdb
• 分子名称: Streptavidin, 5-[(3~{a}~{S},4~{S},6~{a}~{R})-2-oxidanylidene-1,3,3~{a},4,6,6~{a}-hexahydrothieno[3,4-d]imidazol-4-yl]-~{N}-[2-(3,4-dihydro-2~{H}-pyrano[2,3-c]pyridin-6-ylmethylamino)ethyl]pentanamide, MANGANESE (II) ION, ... (6 entities in total)
• 機能のキーワード: artificial meatlloenzyme, transfer hydrogenase, manganese, metal binding protein
• 由来する生物種: Streptomyces avidinii
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 68897.67

構造登録者

Lau, K.,Wang, W.,Pojer, F.,Larabi, A. (登録日: 2023-05-24, 公開日: 2023-09-13, 最終更新日: 2023-10-25)

主引用文献

Wang, W.,Tachibana, R.,Zou, Z.,Chen, D.,Zhang, X.,Lau, K.,Pojer, F.,Ward, T.R.,Hu, X.
Manganese Transfer Hydrogenases Based on the Biotin-Streptavidin Technology.
Angew.Chem.Int.Ed.Engl., 62:e202311896-e202311896, 2023

PubMed Abstract: Artificial (transfer) hydrogenases have been developed for organic synthesis, but they rely on precious metals. Native hydrogenases use Earth-abundant metals, but these cannot be applied for organic synthesis due, in part, to their substrate specificity. Herein, we report the design and development of manganese transfer hydrogenases based on the biotin-streptavidin technology. By incorporating bio-mimetic Mn(I) complexes into the binding cavity of streptavidin, and through chemo-genetic optimization, we have obtained artificial enzymes that hydrogenate ketones with nearly quantitative yield and up to 98 % enantiomeric excess (ee). These enzymes exhibit broad substrate scope and high functional-group tolerance. According to QM/MM calculations and X-ray crystallography, the S112Y mutation, combined with the appropriate chemical structure of the Mn cofactor plays a critical role in the reactivity and enantioselectivity of the artificial metalloenzyme (ArMs). Our work highlights the potential of ArMs incorporating base-meal cofactors for enantioselective organic synthesis.

PubMed: 37671593
DOI: 10.1002/anie.202311896

実験手法

X-RAY DIFFRACTION (1.88 Å)