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| - | [[Image:1erw.jpg|left|200px]] | + | {{Seed}} |
| | + | [[Image:1erw.png|left|200px]] |
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| | {{STRUCTURE_1erw| PDB=1erw | SCENE= }} | | {{STRUCTURE_1erw| PDB=1erw | SCENE= }} |
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| - | '''HUMAN THIOREDOXIN DOUBLE MUTANT WITH CYS 32 REPLACED BY SER AND CYS 35 REPLACED BY SER'''
| + | ===HUMAN THIOREDOXIN DOUBLE MUTANT WITH CYS 32 REPLACED BY SER AND CYS 35 REPLACED BY SER=== |
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| - | ==Overview==
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| - | BACKGROUND: Human thioredoxin reduces the disulfide bonds of numerous proteins in vitro, and can activate transcription factors such as NFkB in vivo. Thioredoxin can also act as a growth factor, and is overexpressed and secreted in certain tumor cells. RESULTS: Crystal structures were determined for reduced and oxidized wild type human thioredoxin (at 1.7 and 2.1 A nominal resolution, respectively), and for reduced mutant proteins Cys73-->Ser and Cys32-->Ser/Cys35-->Ser (at 1.65 and 1.8 A, respectively). Surprisingly, thioredoxin is dimeric in all four structures; the dimer is linked through a disulfide bond between Cys73 of each monomer, except in Cys73-->Ser where a hydrogen bond occurs. The thioredoxin active site is blocked by dimer formation. Conformational changes in the active site and dimer interface accompany oxidation of the active-site cysteines, Cys32 and Cys35. CONCLUSIONS: It has been suggested that a reduced pKa in the first cysteine (Cys32 in human thioredoxin) of the active-site sequence is important for modulation of the redox potential in thioredoxin. A hydrogen bond between the sulfhydryls of Cys32 and Cys35 may reduce the pKa of Cys32 and this pKa depression probably results in increased nucleophilicity of the Cys32 thiolate group. This nucleophilicity, in tum, is thought to be necessary for the role of thioredoxin in disulfide-bond reduction. The physiological role, if any, of thioredoxin dimer formation remains unknown. It is possible that dimerization may provide a mechanism for regulation of the protein, or a means of sensing oxidative stress.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_8805557}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 8805557 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_8805557}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Thioredoxin]] | | [[Category: Thioredoxin]] |
| | [[Category: X-ray crystallography]] | | [[Category: X-ray crystallography]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 15:26:55 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 01:46:43 2008'' |
Revision as of 22:46, 30 June 2008
Template:STRUCTURE 1erw
HUMAN THIOREDOXIN DOUBLE MUTANT WITH CYS 32 REPLACED BY SER AND CYS 35 REPLACED BY SER
Template:ABSTRACT PUBMED 8805557
About this Structure
1ERW is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structures of reduced, oxidized, and mutated human thioredoxins: evidence for a regulatory homodimer., Weichsel A, Gasdaska JR, Powis G, Montfort WR, Structure. 1996 Jun 15;4(6):735-51. PMID:8805557
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