1H6V

Mammalian thioredoxin reductase

1H6V の概要

• エントリーDOI: 10.2210/pdb1h6v/pdb
• 分子名称: THIOREDOXIN REDUCTASE, FLAVIN-ADENINE DINUCLEOTIDE, NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, ... (4 entities in total)
• 機能のキーワード: oxidoreductase, pyridine nucleotide-disulfide oxidoreductase, flavoprotein
• 由来する生物種: RATTUS NORVEGICUS (RAT)
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 337063.66

構造登録者

Sandalova, T.,Zhong, L.,Lindqvist, Y.,Holmgren, A.,Schneider, G. (登録日: 2001-06-27, 公開日: 2001-08-14, 最終更新日: 2024-10-16)

主引用文献

Sandalova, T.,Zhong, L.,Lindqvist, Y.,Holmgren, A.,Schneider, G.
Three-Dimensional Structure of a Mammalian Thioredoxin Reductase: Implication for Mechanism and Evolution of a Selenocysteine Dependent Enzyme
Proc.Natl.Acad.Sci.USA, 98:9533-, 2001

PubMed Abstract: Thioredoxin reductases (TrxRs) from mammalian cells contain an essential selenocysteine residue in the conserved C-terminal sequence Gly-Cys-SeCys-Gly forming a selenenylsulfide in the oxidized enzyme. Reduction by NADPH generates a selenolthiol, which is the active site in reduction of Trx. The three-dimensional structure of the SeCys498Cys mutant of rat TrxR in complex with NADP(+) has been determined to 3.0-A resolution by x-ray crystallography. The overall structure is similar to that of glutathione reductase (GR), including conserved amino acid residues binding the cofactors FAD and NADPH. Surprisingly, all residues directly interacting with the substrate glutathione disulfide in GR are conserved despite the failure of glutathione disulfide to act as a substrate for TrxR. The 16-residue C-terminal tail, which is unique to mammalian TrxR, folds in such a way that it can approach the active site disulfide of the other subunit in the dimer. A model of the complex of TrxR with Trx suggests that electron transfer from NADPH to the disulfide of the substrate is possible without large conformational changes. The C-terminal extension typical of mammalian TrxRs has two functions: (i) it extends the electron transport chain from the catalytic disulfide to the enzyme surface, where it can react with Trx, and (ii) it prevents the enzyme from acting as a GR by blocking the redox-active disulfide. Our results suggest that mammalian TrxR evolved from the GR scaffold rather than from its prokaryotic counterpart. This evolutionary switch renders cell growth dependent on selenium.

PubMed: 11481439
DOI: 10.1073/PNAS.171178698

実験手法

X-RAY DIFFRACTION (3 Å)