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| | {{STRUCTURE_2nvk| PDB=2nvk | SCENE= }} | | {{STRUCTURE_2nvk| PDB=2nvk | SCENE= }} |
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| - | '''Crystal Structure of Thioredoxin Reductase from Drosophila melanogaster'''
| + | ===Crystal Structure of Thioredoxin Reductase from Drosophila melanogaster=== |
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| - | ==Overview==
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| - | Thioredoxin reductase (TR) from Drosophila melanogaster (DmTR) is a member of the glutathione reductase (GR) family of pyridine nucleotide disulfide oxidoreductases and catalyzes the reduction of the redox-active disulfide bond of thioredoxin. DmTR is notable for having high catalytic activity without the presence of a selenocysteine (Sec) residue (which is essential for the mammalian thioredoxin reductases). We report here the X-ray crystal structure of DmTR at 2.4 A resolution (Rwork = 19.8%, Rfree = 24.7%) in which the enzyme was truncated to remove the C-terminal tripeptide sequence Cys-Cys-Ser. We also demonstrate that tetrapeptides equivalent to the oxidized C-terminal active sites of both mouse mitochondrial TR (mTR3) and DmTR are substrates for the truncated forms of both enzymes. This truncated enzyme/peptide substrate system examines the kinetics of the ring-opening step that occurs during the enzymatic cycle of TR. The ring-opening step is 300-500-fold slower when Sec is replaced with Cys in mTR3 when using this system. Conversely, when Cys is replaced with Sec in DmTR, the rate of ring opening is only moderately increased (5-36-fold). Structures of these tetrapeptides were oriented in the active site of both enzymes using oxidized glutathione bound to GR as a template. DmTR has a more open tetrapeptide binding pocket than the mouse enzyme and accommodates the peptide Ser-Cys-Cys-Ser(ox) in a cis conformation that allows for the protonation of the leaving-group Cys by His464', which helps to explain why this TR can function without the need for Sec. In contrast, mTR3 shows a narrower pocket. One possible result of this narrower interface is that the mammalian redox-active tetrapeptide Gly-Cys-Sec-Gly may adopt a trans conformation for a better fit. This places the Sec residue farther away from the protonating histidine residue, but the lower pKa of Sec in comparison to that of Cys eliminates the need for Sec to be protonated.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_17385893}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 17385893 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_17385893}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Oxidoreductase]] | | [[Category: Oxidoreductase]] |
| | [[Category: Rossmann]] | | [[Category: Rossmann]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 09:57:34 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 07:15:03 2008'' |
Revision as of 04:15, 29 July 2008
Crystal Structure of Thioredoxin Reductase from Drosophila melanogaster
Template:ABSTRACT PUBMED 17385893
About this Structure
2NVK is a Single protein structure of sequence from Drosophila melanogaster. Full crystallographic information is available from OCA.
Reference
Structural and biochemical studies reveal differences in the catalytic mechanisms of mammalian and Drosophila melanogaster thioredoxin reductases., Eckenroth BE, Rould MA, Hondal RJ, Everse SJ, Biochemistry. 2007 Apr 24;46(16):4694-705. Epub 2007 Mar 27. PMID:17385893
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