2j3n | pdb_00002j3n

X-RAY STRUCTURE OF HUMAN THIOREDOXIN REDUCTASE 1

spinqualitylabelsall models 2j3n, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2j3n is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: FAD, MPD, NAP Related: 1w1c, 1w1e, 2cfy Activity: Thioredoxin-disulfide reductase, with EC number 1.8.1.9 Resources: FirstGlance, OCA, RCSB, PDBsum Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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 the concerted action of the three side-chain residues of N418, N419 and W407, which act as a guiding bar for the C-terminal sliding process. As supported by previous kinetic data, the three visualized conformations might reflect different stages in enzymatic catalysis. Comparison with other disulfide reductases including human glutathione reductase revealed specific inhibitor binding sites in the intersubunit cavity of hTrxR that can be exploited for structure-based inhibitor development. The structure of human thioredoxin reductase 1 provides insights into C-terminal rearrangements during catalysis.,Fritz-Wolf K, Urig S, Becker K J Mol Biol. 2007 Jun 29;370(1):116-27. Epub 2007 Apr 24. PMID:17512005 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Thioredoxin Reductase

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