1WNT

Structure of the tetrameric form of Human L-Xylulose Reductase

1WNT の概要

• エントリーDOI: 10.2210/pdb1wnt/pdb
• 関連するPDBエントリー: 1PR9
• 分子名称: L-xylulose reductase, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE (3 entities in total)
• 機能のキーワード: 7 stranded parallel beta sheets, 6 alpha helices, rossmann fold, dinucleotide co-enzyme binding motif, oxidoreductase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 106737.75

構造登録者

El-Kabbani, O.,Carbone, V.,Darmanin, C.,Ishikura, S.,Hara, A. (登録日: 2004-08-09, 公開日: 2005-07-19, 最終更新日: 2024-11-13)

主引用文献

El-Kabbani, O.,Carbone, V.,Darmanin, C.,Ishikura, S.,Hara, A.
Structure of the tetrameric form of human L-Xylulose reductase: Probing the inhibitor-binding site with molecular modeling and site-directed mutagenesis
Proteins, 60:424-432, 2005

PubMed Abstract: L-Xylulose reductase (XR) is a member of the short-chain dehydrogenase/reductase (SDR) superfamily. In this study we report the structure of the biological tetramer of human XR in complex with NADP(+) and a competitive inhibitor solved at 2.3 A resolution. A single subunit of human XR is formed by a centrally positioned, seven-stranded, parallel beta-sheet surrounded on either side by two arrays of three alpha-helices. Two helices located away from the main body of the protein form the variable substrate-binding cleft, while the dinucleotide coenzyme-binding motif is formed by a classical Rossmann fold. The tetrameric structure of XR, which is held together via salt bridges formed by the guanidino group of Arg203 from one monomer and the carboxylate group of the C-terminal residue Cys244 from the neighboring monomer, explains the ability of human XR to prevent the cold inactivation seen in the rodent forms of the enzyme. The orientations of Arg203 and Cys244 are maintained by a network of hydrogen bonds and main-chain interactions of Gln137, Glu238, Phe241, and Trp242. These interactions are similar to those defining the quaternary structure of the closely related carbonyl reductase from mouse lung. Molecular modeling and site-directed mutagenesis identified the active site residues His146 and Trp191 as forming essential contacts with inhibitors of XR. These results could provide a structural basis in the design of potent and specific inhibitors for human XR.

PubMed: 15906319
DOI: 10.1002/prot.20487

実験手法

X-RAY DIFFRACTION (2.3 Å)