1mdk: Difference between revisions
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|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY=[[1mdi|1MDI]], [[1mdj|1MDJ]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1mdk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mdk OCA], [http://www.ebi.ac.uk/pdbsum/1mdk PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1mdk RCSB]</span> | |||
}} | }} | ||
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==Overview== | ==Overview== | ||
BACKGROUND: Human thioredoxin is a 12 kDa cellular redox protein that plays a key role in maintaining the redox environment of the cell. It has recently been shown to be responsible for activating the DNA-binding properties of the cellular transcription factor, NF kappa B, by reducing a disulfide bond involving Cys62 of the p50 subunit. Using multidimensional heteronuclear-edited and hetero-nuclear-filtered NMR spectroscopy, we have solved the solution structure of a complex of human thioredoxin and a 13-residue peptide extending from residues 56-68 of p50, representing a kinetically stable mixed disulfide intermediate along the reaction pathway. RESULTS: The NF kappa B peptide is located in a long boot-shaped cleft on the surface of human thioredoxin delineated by the active-site loop, helices alpha 2, alpha 3 and alpha 4, and strands beta 3 and beta 4. The peptide adopts a crescent-like conformation with a smooth 110 degrees bend centered around residue 60 which permits it to follow the path of the cleft. CONCLUSIONS: In addition to the intermolecular disulfide bridge between Cys32 of human thioredoxin and Cys62 of the peptide, the complex is stabilized by numerous hydrogen-bonding, electrostatic and hydrophobic interactions which involve residues 57-65 of the NF kappa B peptide and confer substrate specificity. These structural features permit one to suggest the specificity requirements for human thioredoxin-catalyzed disulfide bond reduction of proteins. | BACKGROUND: Human thioredoxin is a 12 kDa cellular redox protein that plays a key role in maintaining the redox environment of the cell. It has recently been shown to be responsible for activating the DNA-binding properties of the cellular transcription factor, NF kappa B, by reducing a disulfide bond involving Cys62 of the p50 subunit. Using multidimensional heteronuclear-edited and hetero-nuclear-filtered NMR spectroscopy, we have solved the solution structure of a complex of human thioredoxin and a 13-residue peptide extending from residues 56-68 of p50, representing a kinetically stable mixed disulfide intermediate along the reaction pathway. RESULTS: The NF kappa B peptide is located in a long boot-shaped cleft on the surface of human thioredoxin delineated by the active-site loop, helices alpha 2, alpha 3 and alpha 4, and strands beta 3 and beta 4. The peptide adopts a crescent-like conformation with a smooth 110 degrees bend centered around residue 60 which permits it to follow the path of the cleft. CONCLUSIONS: In addition to the intermolecular disulfide bridge between Cys32 of human thioredoxin and Cys62 of the peptide, the complex is stabilized by numerous hydrogen-bonding, electrostatic and hydrophobic interactions which involve residues 57-65 of the NF kappa B peptide and confer substrate specificity. These structural features permit one to suggest the specificity requirements for human thioredoxin-catalyzed disulfide bond reduction of proteins. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: complex (electron transport/peptide)]] | [[Category: complex (electron transport/peptide)]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:14:42 2008'' | ||
