5GWT

4-hydroxyisoleucine dehydrogenase mutant complexed with NADH and succinate

5GWT の概要

• エントリーDOI: 10.2210/pdb5gwt/pdb
• 関連するPDBエントリー: 5GWR 5GWS
• 分子名称: 4-hydroxyisolecuine dehydrogenase, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, SUCCINIC ACID, ... (4 entities in total)
• 機能のキーワード: nadh-dependent, short-chain, dehydrogenase, reductase, oxidoreductase
• 由来する生物種: Bacillus thuringiensis
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 126312.69

構造登録者

Shi, X.,Miyakawa, T.,Nakamura, A.,Tanokura, M. (登録日: 2016-09-13, 公開日: 2017-10-25, 最終更新日: 2023-11-08)

主引用文献

Shi, X.,Miyakawa, T.,Nakamura, A.,Hou, F.,Hibi, M.,Ogawa, J.,Kwon, Y.,Tanokura, M.
Engineering a short-chain dehydrogenase/reductase for the stereoselective production of (2S,3R,4S)-4-hydroxyisoleucine with three asymmetric centers.
Sci Rep, 7:13703-13703, 2017

PubMed Abstract: Fenugreek is a dietary supplement for anti-aging and human health. (2S,3R,4S)-4-hydroxyisoleucine (4-HIL), which is extracted from fenugreek seeds, is expected to be a promising orally active drug for diabetes and diabetic nephropathy because of its insulinotropic effect. Although several chemical synthesis methods of 4-HIL have been proposed, these methods require multistep reactions to control the stereochemistry of 4-HIL. In this study, we modified the key enzyme 4-HIL dehydrogenase (HILDH) to overcome the biggest limitation in commercial-scale production of 4-HIL. As a result, an effective one-step carbonyl reduction to produce (2S,3R,4S)-4-HIL was successfully accomplished with strict stereoselectivity (>99% de). Mass production of (2S,3R,4S)-4-HIL by our synthetic method could have a significant contribution to the prevention of diabetes, dyslipidemia, and Alzheimer's disease. (120 words/200 words).

PubMed: 29057974
DOI: 10.1038/s41598-017-13978-w

実験手法

X-RAY DIFFRACTION (1.9 Å)