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PDBsum entry 4jii
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Oxidoreductase/oxidoreductase inhibitor
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PDB id
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4jii
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PDB id:
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| Name: |
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Oxidoreductase/oxidoreductase inhibitor
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Title:
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Crystal structure of akr1b10 complexed with NADP+ and zopolrestat
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Structure:
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Aldo-keto reductase family 1 member b10. Chain: x. Synonym: arl-1, aldose reductase-like, aldose reductase-related protein, arp, harp, small intestine reductase, si reductase. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: akr1b10, akr1b11. Expressed in: escherichia coli. Expression_system_taxid: 511693.
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Resolution:
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2.20Å
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R-factor:
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0.172
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R-free:
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0.218
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Authors:
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L.Zhang,X.Zheng,H.Zhang,Y.Zhao,K.Chen,J.Zhai,X.Hu,Structural Genomics Consortium (Sgc)
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Key ref:
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L.Zhang
et al.
(2013).
Inhibitor selectivity between aldo-keto reductase superfamily members AKR1B10 and AKR1B1: role of Trp112 (Trp111).
Febs Lett,
587,
3681-3686.
PubMed id:
DOI:
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Date:
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06-Mar-13
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Release date:
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23-Oct-13
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PROCHECK
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Headers
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References
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O60218
(AK1BA_HUMAN) -
Aldo-keto reductase family 1 member B10 from Homo sapiens
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Seq:
Struc:
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316 a.a.
318 a.a.*
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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*
PDB and UniProt seqs differ
at 1 residue position (black
cross)
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Enzyme class 1:
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E.C.1.1.1.300
- NADP-retinol dehydrogenase.
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Reaction:
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all-trans-retinol + NADP+ = all-trans-retinal + NADPH + H+
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all-trans-retinol
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+
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NADP(+)
Bound ligand (Het Group name = )
corresponds exactly
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=
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all-trans-retinal
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+
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NADPH
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+
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H(+)
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Enzyme class 2:
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E.C.1.1.1.54
- allyl-alcohol dehydrogenase.
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Reaction:
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allyl alcohol + NADP+ = acrolein + NADPH + H+
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allyl alcohol
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+
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NADP(+)
Bound ligand (Het Group name = )
corresponds exactly
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=
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acrolein
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+
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NADPH
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+
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H(+)
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Note, where more than one E.C. class is given (as above), each may
correspond to a different protein domain or, in the case of polyprotein
precursors, to a different mature protein.
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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DOI no:
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Febs Lett
587:3681-3686
(2013)
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PubMed id:
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Inhibitor selectivity between aldo-keto reductase superfamily members AKR1B10 and AKR1B1: role of Trp112 (Trp111).
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L.Zhang,
H.Zhang,
Y.Zhao,
Z.Li,
S.Chen,
J.Zhai,
Y.Chen,
W.Xie,
Z.Wang,
Q.Li,
X.Zheng,
X.Hu.
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ABSTRACT
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The antineoplastic target aldo-keto reductase family member 1B10 (AKR1B10) and
the critical polyol pathway enzyme aldose reductase (AKR1B1) share high
structural similarity. Crystal structures reported here reveal a surprising
Trp112 native conformation stabilized by a specific Gln114-centered hydrogen
bond network in the AKR1B10 holoenzyme, and suggest that AKR1B1 inhibitors could
retain their binding affinities toward AKR1B10 by inducing Trp112 flip to result
in an "AKR1B1-like" active site in AKR1B10, while selective AKR1B10
inhibitors can take advantage of the broader active site of AKR1B10 provided by
the native Trp112 side-chain orientation.
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