1mdk

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[[Image:1mdk.gif|left|200px]]<br /><applet load="1mdk" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1mdk.gif|left|200px]]
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caption="1mdk" />
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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)'''<br />
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{{Structure
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|PDB= 1mdk |SIZE=350|CAPTION= <scene name='initialview01'>1mdk</scene>
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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)'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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1MDK is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MDK OCA].
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1MDK is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MDK OCA].
==Reference==
==Reference==
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=7788295 7788295]
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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:[http://www.ncbi.nlm.nih.gov/pubmed/7788295 7788295]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Protein complex]]
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[[Category: complex (electron transport/peptide)]]
[[Category: complex (electron transport/peptide)]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:54:09 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:42:11 2008''

Revision as of 10:42, 20 March 2008


PDB ID 1mdk

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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)


Contents

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.

Disease

Known disease associated with this structure: Ciliary dyskinesia, primary, 6 OMIM:[607421]

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

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