1mdk: Difference between revisions
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New page: left|200px<br /> <applet load="1mdk" size="450" color="white" frame="true" align="right" spinBox="true" caption="1mdk" /> '''HIGH RESOLUTION SOLUTION NMR STRUCTURE OF M... |
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[[Image:1mdk.gif|left|200px]]<br /> | [[Image:1mdk.gif|left|200px]]<br /><applet load="1mdk" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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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 /> | '''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 /> | ||
==Overview== | ==Overview== | ||
BACKGROUND: Human thioredoxin is a 12 kDa cellular redox protein that | 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== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
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:// | 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]. | ||
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Clore, G | [[Category: Clore, G M.]] | ||
[[Category: Gronenborn, A | [[Category: Gronenborn, A M.]] | ||
[[Category: Qin, J.]] | [[Category: Qin, J.]] | ||
[[Category: complex (electron transport/peptide)]] | [[Category: complex (electron transport/peptide)]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:54:09 2008'' | ||
