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| {{STRUCTURE_1mdi| PDB=1mdi | SCENE= }} | | {{STRUCTURE_1mdi| PDB=1mdi | SCENE= }} |
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| '''HIGH RESOLUTION SOLUTION NMR STRUCTURE OF MIXED DISULFIDE INTERMEDIATE BETWEEN MUTANT HUMAN THIOREDOXIN AND A 13 RESIDUE PEPTIDE COMPRISING ITS TARGET SITE IN HUMAN NFKB'''
| | ===HIGH RESOLUTION SOLUTION NMR STRUCTURE OF MIXED DISULFIDE INTERMEDIATE BETWEEN MUTANT HUMAN THIOREDOXIN AND A 13 RESIDUE PEPTIDE COMPRISING ITS TARGET SITE IN HUMAN NFKB=== |
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| ==Overview==
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| 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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_7788295}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 7788295 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_7788295}} |
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| ==About this Structure== | | ==About this Structure== |
| 1MDI 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=1MDI OCA]. | | 1MDI is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MDI OCA]. |
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| ==Reference== | | ==Reference== |
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| [[Category: Gronenborn, A M.]] | | [[Category: Gronenborn, A M.]] |
| [[Category: Qin, J.]] | | [[Category: Qin, J.]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 00:54:50 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 2 23:44:01 2008'' |
