1ZDL

Crystal Structure of Mouse Thioredoxin Reductase Type 2

1ZDL の概要

• エントリーDOI: 10.2210/pdb1zdl/pdb
• 関連するPDBエントリー: 1H6V 3GRS
• 分子名称: Thioredoxin reductase 2, mitochondrial, FLAVIN-ADENINE DINUCLEOTIDE, NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, ... (4 entities in total)
• 機能のキーワード: selenocysteine, thioredoxin, reductase, flavoprotein, oxidoreductase
• 由来する生物種: Mus musculus (house mouse)
• 細胞内の位置: Mitochondrion : Q9JLT4
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 57347.53

構造登録者

Biterova, E.I.,Turanov, A.A.,Gladyshev, V.N.,Barycki, J.J. (登録日: 2005-04-14, 公開日: 2005-11-01, 最終更新日: 2024-10-09)

主引用文献

Biterova, E.I.,Turanov, A.A.,Gladyshev, V.N.,Barycki, J.J.
Crystal structures of oxidized and reduced mitochondrial thioredoxin reductase provide molecular details of the reaction mechanism.
Proc.Natl.Acad.Sci.Usa, 102:15018-15023, 2005

PubMed Abstract: Thioredoxin reductase (TrxR) is an essential enzyme required for the efficient maintenance of the cellular redox homeostasis, particularly in cancer cells that are sensitive to reactive oxygen species. In mammals, distinct isozymes function in the cytosol and mitochondria. Through an intricate mechanism, these enzymes transfer reducing equivalents from NADPH to bound FAD and subsequently to an active-site disulfide. In mammalian TrxRs, the dithiol then reduces a mobile C-terminal selenocysteine-containing tetrapeptide of the opposing subunit of the dimer. Once activated, the C-terminal redox center reduces a disulfide bond within thioredoxin. In this report, we present the structural data on a mitochondrial TrxR, TrxR2 (also known as TR3 and TxnRd2). Mouse TrxR2, in which the essential selenocysteine residue had been replaced with cysteine, was isolated as a FAD-containing holoenzyme and crystallized (2.6 A; R = 22.2%; R(free) = 27.6%). The addition of NADPH to the TrxR2 crystals resulted in a color change, indicating reduction of the active-site disulfide and formation of a species presumed to be the flavin-thiolate charge transfer complex. Examination of the NADP(H)-bound model (3.0 A; R = 24.1%; R(free) = 31.2%) indicates that an active-site tyrosine residue must rotate from its initial position to stack against the nicotinamide ring of NADPH, which is juxtaposed to the isoalloxazine ring of FAD to facilitate hydride transfer. Detailed analysis of the structural data in conjunction with a model of the unusual C-terminal selenenylsulfide suggests molecular details of the reaction mechanism and highlights evolutionary adaptations among reductases.

PubMed: 16217027
DOI: 10.1073/pnas.0504218102

実験手法

X-RAY DIFFRACTION (3 Å)