2j3n: Difference between revisions
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==Overview== | ==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, ... | 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== | ==About this Structure== | ||
2J3N is a | 2J3N is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with FAD, NAP and MPD as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2J3N OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: selenocysteine]] | [[Category: selenocysteine]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 14:07:32 2007'' | ||
