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PDBsum entry 5yap
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Oxidoreductase
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PDB id
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5yap
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References listed in PDB file
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Key reference
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Title
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Structural basis of l-Glucose oxidation by scyllo-Inositol dehydrogenase: implications for a novel enzyme subfamily classification.
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Authors
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K.Fukano,
K.Ozawa,
M.Kokubu,
T.Shimizu,
S.Ito,
Y.Sasaki,
A.Nakamura,
S.Yajima.
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Ref.
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PLoS One, 2018,
13,
e0198010.
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PubMed id
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Note: In the PDB file this reference is
annotated as "TO BE PUBLISHED". The citation details given above have
been manually determined.
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Abstract
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For about 70 years, L-glucose had been considered non-metabolizable by either
mammalian or bacterial cells. Recently, however, an L-glucose catabolic pathway
has been discovered in Paracoccus laeviglucosivorans, and the genes responsible
cloned. Scyllo-inositol dehydrogenase is involved in the first step in the
pathway that oxidizes L-glucose to produce L-glucono-1,5-lactone with
concomitant reduction of NAD+ dependent manner. Here, we report the crystal
structure of the ternary complex of scyllo-inositol dehydrogenase with NAD+ and
L-glucono-1,5-lactone at 1.8 Å resolution. The enzyme adopts a homo-tetrameric
structure, similar to those of the inositol dehydrogenase family, and the
electron densities of the bound sugar was clearly observed, allowing
identification of the residues responsible for interaction with the substrate in
the catalytic site. In addition to the conserved catalytic residues (Lys106,
Asp191, and His195), another residue, His318, located in the loop region of the
adjacent subunit, is involved in substrate recognition. Site-directed
mutagenesis confirmed the role of these residues in catalytic activity. We also
report the complex structures of the enzyme with myo-inositol and
scyllo-inosose. The Arg178 residue located in the flexible loop at the entrance
of the catalytic site is also involved in substrate recognition, and plays an
important role in accepting both L-glucose and inositols as substrates. On the
basis of these structural features, which have not been identified in the known
inositol dehydrogenases, and a phylogenetic analysis of IDH family enzymes, we
suggest a novel subfamily of the GFO/IDH/MocA family. Since many enzymes in this
family have not biochemically characterized, our results could promote to find
their activities with various substrates.
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