3QFB

Crystal structure of the human thioredoxin reductase-thioredoxin complex

Summary for 3QFB

• Entry DOI: 10.2210/pdb3qfb/pdb
• Related: 3QFA
• Descriptor: Thioredoxin reductase 1, cytoplasmic, Thioredoxin, FLAVIN-ADENINE DINUCLEOTIDE, ... (5 entities in total)
• Functional Keywords: protein-protein complex, rossmann fold, thioredoxin fold, homodimeric pyridine nucleotide disulfide oxidoreductase, electron transport, oxidoreductase
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm (By similarity). Isoform 4: Cytoplasm. Isoform 5: Cytoplasm: Q16881; Nucleus: P10599
• Total number of polymer chains: 4
• Total formula weight: 141960.64

Authors

Fritz-Wolf, K.,Kehr, S.,Stumpf, M.,Rahlfs, S.,Becker, K. (deposition date: 2011-01-21, release date: 2011-07-27, Last modification date: 2024-10-30)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.6 Å)