3QFA

Crystal structure of the human thioredoxin reductase-thioredoxin complex

3QFA の概要

• エントリーDOI: 10.2210/pdb3qfa/pdb
• 関連するPDBエントリー: 3QFB
• 分子名称: Thioredoxin reductase 1, cytoplasmic, Thioredoxin, FLAVIN-ADENINE DINUCLEOTIDE, ... (5 entities in total)
• 機能のキーワード: protein-protein complex, rossmann fold, thioredoxin fold, homodimeric pyridine nucleotide disulfide oxidoreductase, electron transport, oxidoreductase
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm (By similarity). Isoform 4: Cytoplasm. Isoform 5: Cytoplasm: Q16881; Nucleus: P10599
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 141960.64

構造登録者

Fritz-Wolf, K.,Kehr, S.,Stumpf, M.,Rahlfs, S.,Becker, K. (登録日: 2011-01-21, 公開日: 2011-07-27, 最終更新日: 2024-10-30)

主引用文献

Fritz-Wolf, K.,Kehr, S.,Stumpf, M.,Rahlfs, S.,Becker, K.
Crystal structure of the human thioredoxin reductase-thioredoxin complex
Nat Commun, 2:383-383, 2011

PubMed Abstract: Thioredoxin reductase 1 (TrxR1) is a homodimeric flavoprotein crucially involved in the regulation of cellular redox homeostasis, growth, and differentiation. Its importance in various diseases makes TrxR1 a highly interesting drug target. Here we present the first crystal structures of human TrxR1 in complex with its substrate thioredoxin (Trx). The carboxy-terminal redox centre is found about 20 Å apart from the amino-terminal redox centre, with no major conformational changes in TrxR or Trx. Thus, our structure confirms that the enzyme uses a flexible C-terminal arm for electron transport to its substrates, which is stabilized by a guiding bar for controlled transfer. This notion is supported by mutational analyses. Furthermore, essential residues of the interface region were characterized both structurally and functionally. The structure provides templates for future drug design, and contributes to our understanding of redox regulatory processes in mammals.

PubMed: 21750537
DOI: 10.1038/ncomms1382

実験手法

X-RAY DIFFRACTION (2.2 Å)