1mdk
From Proteopedia
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'''HIGH RESOLUTION SOLUTION NMR STRUCTURE OF MIXED DISULFIDE INTERMEDIATE BETWEEN HUMAN THIOREDOXIN (C35A, C62A, C69A, C73A) MUTANT AND A 13 RESIDUE PEPTIDE COMPRISING ITS TARGET SITE IN HUMAN NFKB (RESIDUES 56-68 OF THE P50 SUBUNIT OF NFKB)''' | '''HIGH RESOLUTION SOLUTION NMR STRUCTURE OF MIXED DISULFIDE INTERMEDIATE BETWEEN HUMAN THIOREDOXIN (C35A, C62A, C69A, C73A) MUTANT AND A 13 RESIDUE PEPTIDE COMPRISING ITS TARGET SITE IN HUMAN NFKB (RESIDUES 56-68 OF THE P50 SUBUNIT OF NFKB)''' | ||
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[[Category: Gronenborn, A M.]] | [[Category: Gronenborn, A M.]] | ||
[[Category: Qin, J.]] | [[Category: Qin, J.]] | ||
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Revision as of 21:54, 2 May 2008
HIGH RESOLUTION SOLUTION NMR STRUCTURE OF MIXED DISULFIDE INTERMEDIATE BETWEEN HUMAN THIOREDOXIN (C35A, C62A, C69A, C73A) MUTANT AND A 13 RESIDUE PEPTIDE COMPRISING ITS TARGET SITE IN HUMAN NFKB (RESIDUES 56-68 OF THE P50 SUBUNIT OF NFKB)
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.
About this Structure
1MDK is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Solution structure of human thioredoxin in a mixed disulfide intermediate complex with its target peptide from the transcription factor NF kappa B., Qin J, Clore GM, Kennedy WM, Huth JR, Gronenborn AM, Structure. 1995 Mar 15;3(3):289-97. PMID:7788295 Page seeded by OCA on Sat May 3 00:54:52 2008
