5GWS

4-hydroxyisoleucine dehydrogenase complexed with NADH and succinate

Summary for 5GWS

• Entry DOI: 10.2210/pdb5gws/pdb
• Related: 5GWR 5GWT
• Descriptor: 4-hydroxyisolecuine dehydrogenase, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, SUCCINIC ACID, ... (4 entities in total)
• Functional Keywords: nadh-dependent, short-chain, dehydrogenase, reductase, oxidoreductase
• Biological source: Bacillus thuringiensis
• Total number of polymer chains: 4
• Total formula weight: 128434.99

Authors

Shi, X.,Miyakawa, T.,Nakamura, A.,Tanokura, M. (deposition date: 2016-09-13, release date: 2017-10-25, Last modification date: 2023-11-08)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.35 Å)