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PDBsum entry 1k8c
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Oxidoreductase
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PDB id
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1k8c
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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The structure of apo and holo forms of xylose reductase, A dimeric aldo-Keto reductase from candida tenuis.
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Authors
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K.L.Kavanagh,
M.Klimacek,
B.Nidetzky,
D.K.Wilson.
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Ref.
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Biochemistry, 2002,
41,
8785-8795.
[DOI no: ]
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PubMed id
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Abstract
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Xylose reductase is a homodimeric oxidoreductase dependent on NADPH or NADH and
belongs to the largely monomeric aldo-keto reductase superfamily of proteins. It
catalyzes the first step in the assimilation of xylose, an aldose found to be a
major constituent monosaccharide of renewable plant hemicellulosic material,
into yeast metabolic pathways. It does this by reducing open chain xylose to
xylitol, which is reoxidized to xylulose by xylitol dehydrogenase and
metabolically integrated via the pentose phosphate pathway. No structure has yet
been determined for a xylose reductase, a dimeric aldo-keto reductase or a
family 2 aldo-keto reductase. The structures of the Candida tenuis xylose
reductase apo- and holoenzyme, which crystallize in spacegroup C2 with different
unit cells, have been determined to 2.2 A resolution and an R-factor of 17.9 and
20.8%, respectively. Residues responsible for mediating the novel dimeric
interface include Asp-178, Arg-181, Lys-202, Phe-206, Trp-313, and Pro-319.
Alignments with other superfamily members indicate that these interactions are
conserved in other dimeric xylose reductases but not throughout the remainder of
the oligomeric aldo-keto reductases, predicting alternate modes of
oligomerization for other families. An arrangement of side chains in a catalytic
triad shows that Tyr-52 has a conserved function as a general acid. The loop
that folds over the NAD(P)H cosubstrate is disordered in the apo form but
becomes ordered upon cosubstrate binding. A slow conformational isomerization of
this loop probably accounts for the observed rate-limiting step involving
release of cosubstrate. Xylose binding (K(m) = 87 mM) is mediated by
interactions with a binding pocket that is more polar than a typical aldo-keto
reductase. Modeling of xylose into the active site of the holoenzyme using
ordered waters as a guide for sugar hydroxyls suggests a convincing mode of
substrate binding.
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