1K8C

Crystal structure of dimeric xylose reductase in complex with NADP(H)

1K8C の概要

• エントリーDOI: 10.2210/pdb1k8c/pdb
• 関連するPDBエントリー: 1JEZ
• 分子名称: xylose reductase, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE (3 entities in total)
• 機能のキーワード: beta-alpha barrel, aldo-keto reductase, nadp(h), oxidoreductase
• 由来する生物種: Candida tenuis
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 147222.42

構造登録者

Kavanagh, K.L.,Klimacek, M.,Nidetzky, B.,Wilson, D.K. (登録日: 2001-10-23, 公開日: 2002-07-05, 最終更新日: 2024-04-03)

主引用文献

Kavanagh, K.L.,Klimacek, M.,Nidetzky, B.,Wilson, D.K.
The structure of apo and holo forms of xylose reductase, a dimeric aldo-keto reductase from Candida tenuis.
Biochemistry, 41:8785-8795, 2002

PubMed Abstract: 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.

PubMed: 12102621
DOI: 10.1021/bi025786n

実験手法

X-RAY DIFFRACTION (2.1 Å)