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PDBsum entry 5gwt
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Oxidoreductase
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PDB id
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5gwt
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PDB id:
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| Name: |
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Oxidoreductase
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Title:
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4-hydroxyisoleucine dehydrogenase mutant complexed with nadh and succinate
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Structure:
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4-hydroxyisolecuine dehydrogenase. Chain: a, b, c, d. Engineered: yes. Mutation: yes
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Source:
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Bacillus thuringiensis. Organism_taxid: 1428. Strain: 2e2. Gene: ac241_05390. Expressed in: escherichia coli. Expression_system_taxid: 562
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Resolution:
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1.90Å
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R-factor:
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0.175
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R-free:
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0.201
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Authors:
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X.Shi,T.Miyakawa,A.Nakamura,M.Tanokura
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Key ref:
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X.Shi
et al.
(2017).
Engineering a short-chain dehydrogenase/reductase for the stereoselective production of (2S,3R,4S)-4-hydroxyisoleucine with three asymmetric centers.
Sci Rep,
7,
13703.
PubMed id:
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Date:
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13-Sep-16
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Release date:
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25-Oct-17
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PROCHECK
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Headers
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References
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Sci Rep
7:13703
(2017)
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PubMed id:
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Engineering a short-chain dehydrogenase/reductase for the stereoselective production of (2S,3R,4S)-4-hydroxyisoleucine with three asymmetric centers.
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X.Shi,
T.Miyakawa,
A.Nakamura,
F.Hou,
M.Hibi,
J.Ogawa,
Y.Kwon,
M.Tanokura.
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ABSTRACT
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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).
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Links
