2j3n

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[[Image:2j3n.jpg|left|200px]]
[[Image:2j3n.jpg|left|200px]]
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{{Structure
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<!--
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|PDB= 2j3n |SIZE=350|CAPTION= <scene name='initialview01'>2j3n</scene>, resolution 2.80&Aring;
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The line below this paragraph, containing "STRUCTURE_2j3n", creates the "Structure Box" on the page.
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|SITE= <scene name='pdbsite=AC1:Mpd+Binding+Site+For+Chain+F'>AC1</scene>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Thioredoxin-disulfide_reductase Thioredoxin-disulfide reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.8.1.9 1.8.1.9] </span>
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or leave the SCENE parameter empty for the default display.
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|GENE=
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-->
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|DOMAIN=
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{{STRUCTURE_2j3n| PDB=2j3n | SCENE= }}
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|RELATEDENTRY=
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2j3n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j3n OCA], [http://www.ebi.ac.uk/pdbsum/2j3n PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2j3n RCSB]</span>
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}}
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'''X-RAY STRUCTURE OF HUMAN THIOREDOXIN REDUCTASE 1'''
'''X-RAY STRUCTURE OF HUMAN THIOREDOXIN REDUCTASE 1'''
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[[Category: Fritz-Wolf, K.]]
[[Category: Fritz-Wolf, K.]]
[[Category: Urig, S.]]
[[Category: Urig, S.]]
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[[Category: cytoplasm]]
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[[Category: Cytoplasm]]
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[[Category: electron transport]]
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[[Category: Electron transport]]
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[[Category: fad]]
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[[Category: Fad]]
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[[Category: flavoprotein]]
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[[Category: Flavoprotein]]
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[[Category: human]]
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[[Category: Human]]
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[[Category: nadp]]
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[[Category: Nadp]]
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[[Category: oxidoreductase]]
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[[Category: Oxidoreductase]]
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[[Category: phosphorylation]]
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[[Category: Phosphorylation]]
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[[Category: pyridine nucleotide dependent disulfide reductase]]
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[[Category: Pyridine nucleotide dependent disulfide reductase]]
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[[Category: redox regulation]]
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[[Category: Redox regulation]]
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[[Category: redox-active center]]
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[[Category: Redox-active center]]
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[[Category: selenium]]
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[[Category: Selenium]]
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[[Category: selenocysteine]]
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[[Category: Selenocysteine]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 08:17:10 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:52:25 2008''
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Revision as of 05:17, 4 May 2008

Template:STRUCTURE 2j3n

X-RAY STRUCTURE OF HUMAN THIOREDOXIN REDUCTASE 1


Overview

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.

About this Structure

2J3N is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

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 Page seeded by OCA on Sun May 4 08:17:10 2008

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