%0 Journal Article %1 FritzWolf.20070629 %A Fritz-Wolf, Karin %A Urig, Sabine %A Becker, Katja %D 2007/06/29/ %J J Mol Biol %K Animals Binding_Sites Crystallography Cysteine Enzyme_Inhibitors Humans IFZ Models Molecular Molecular_Sequence_Data NADP Oxidation-Reduction Protein_Structure Quaternary Thioredoxin-Disulfide_Reductase X-Ray catalysis thioredoxin_reductase_1 %N 1 %P 116-127 %T The structure of human thioredoxin reductase 1 provides insights into C-terminal rearrangements during catalysis %V 370 %X Human thioredoxin reductase (hTrxR) is a homodimeric flavoprotein crucially involved in the regulation of cellular redox reactions, growth and differentiation. The enzyme contains a selenocysteine residue at its C-terminal active site that is essential for catalysis. This redox center is located on a flexible arm, solvent-exposed and reactive towards electrophilic inhibitors, thus representing a target for antitumor drug development. During catalysis reducing equivalents are transferred from the cofactor NADPH to FAD, then to the N-terminal active site cysteine residues and from there to the flexible C-terminal part of the other subunit to be finally delivered to a variety of second substrates at the molecule's surface. Here we report the first crystal structure of hTrxR1 (Sec-->Cys) in complex with FAD and NADP(+) at a resolution of 2.8 A. From the crystals three different conformations of the carboxy-terminal arm could be deduced. The predicted movement of the arm is facilitated by t

@article{FritzWolf.20070629, abstract = {Human thioredoxin reductase (hTrxR) is a homodimeric flavoprotein crucially involved in the regulation of cellular redox reactions, growth and differentiation. The enzyme contains a selenocysteine residue at its C-terminal active site that is essential for catalysis. This redox center is located on a flexible arm, solvent-exposed and reactive towards electrophilic inhibitors, thus representing a target for antitumor drug development. During catalysis reducing equivalents are transferred from the cofactor NADPH to FAD, then to the N-terminal active site cysteine residues and from there to the flexible C-terminal part of the other subunit to be finally delivered to a variety of second substrates at the molecule's surface. Here we report the first crystal structure of hTrxR1 (Sec-->Cys) in complex with FAD and NADP(+) at a resolution of 2.8 A. From the crystals three different conformations of the carboxy-terminal arm could be deduced. The predicted movement of the arm is facilitated by t}, added-at = {2008-10-14T16:07:18.000+0200}, author = {Fritz-Wolf, Karin and Urig, Sabine and Becker, Katja}, biburl = {https://www.bibsonomy.org/bibtex/26093486f32244a6d56e220871c8e0959/nutribiochem}, interhash = {6eb5e04047158ff72a45691f7f9fe055}, intrahash = {6093486f32244a6d56e220871c8e0959}, journal = {J Mol Biol}, keywords = {Animals Binding_Sites Crystallography Cysteine Enzyme_Inhibitors Humans IFZ Models Molecular Molecular_Sequence_Data NADP Oxidation-Reduction Protein_Structure Quaternary Thioredoxin-Disulfide_Reductase X-Ray catalysis thioredoxin_reductase_1}, number = 1, pages = {116-127}, timestamp = {2008-10-14T16:08:41.000+0200}, title = {The structure of human thioredoxin reductase 1 provides insights into C-terminal rearrangements during catalysis}, volume = 370, year = {2007/06/29/} }