1cqh: Difference between revisions
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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 REF-1 (RESIDUES 59-71 OF THE P50 SUBUNIT OF NFKB), NMR, MINIMIZED AVERAGE STRUCTURE'''<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 REF-1 (RESIDUES 59-71 OF THE P50 SUBUNIT OF NFKB), NMR, MINIMIZED AVERAGE STRUCTURE'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
1CQH is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/DNA-(apurinic_or_apyrimidinic_site)_lyase DNA-(apurinic or apyrimidinic site) lyase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.99.18 4.2.99.18] Full crystallographic information is available from [http:// | 1CQH is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/DNA-(apurinic_or_apyrimidinic_site)_lyase DNA-(apurinic or apyrimidinic site) lyase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.99.18 4.2.99.18] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CQH OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: electron transport/peptide]] | [[Category: electron transport/peptide]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 15:36:39 2008'' | ||
Revision as of 16:36, 15 February 2008
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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 REF-1 (RESIDUES 59-71 OF THE P50 SUBUNIT OF NFKB), NMR, MINIMIZED AVERAGE STRUCTURE
OverviewOverview
BACKGROUND: Human thioredoxin (hTRX) is a 12 kDa cellular redox protein, that has been shown to play an important role in the activation of a, number of transcriptional and translational regulators via a thiol-redox, mechanism. This activity may be direct or indirect via another redox, protein known as Ref-1. The structure of a complex of hTRX with a peptide, comprising its target from the transcription factor NF kappa B has, previously been solved. To further extend our knowledge of the recognition, by and interaction of hTRX with its various targets, we have studied a, complex between hTRX and a Ref-1 peptide. This complex represents a, kinetically stable mixed disulfide intermediate along the reaction, pathway. RESULTS: Using multidimensional heteronuclear edited and filtered, NMR spectroscopy, we have solved the solution structure of a complex, between hTRX and a 13-residue peptide comprising residues 59-71 of Ref-1., The Ref-1 peptide is located in a crescent-shaped groove on the surface of, hTRX, the groove being formed by residues in the active-site loop, (residues 32-36), helix 3, beta strands 3 and 5, and the loop between beta, strands 3 and 4. The complex is stabilized by numerous hydrogen-bonding, and hydrophobic interactions that involve residues 61-69 of the peptide, and confer substrate specificity. CONCLUSIONS: The orientation of the, Ref-1 peptide in the hTRX-Ref-1 complex is opposite to that found in the, previously solved complex of hTRX with the target peptide from the, transcription factor NF kappa B. Orientation is determined by three, discriminating interactions involving the nature of the residues at the, P-2' P-4 and P-5 binding positions. (P0 defines the active cysteine of the, peptide, Cys65 for Ref-1 and Cys62 for NF kappa B. Positive and negative, numbers indicate residues N-terminal and C-terminal to this residue, respectively, and vice versa for NF kappa B as it binds in the opposite, orientation.) The environment surrounding the reactive Cys32 of hTRX, as, well as the packing of the P+3 to P-4 residues are essentially the same in, the two complexes, despite the opposing orientation of the peptide chains., This versatility in substrate recognition permits hTRX to act as a, wide-ranging redox regulator for the cell.
DiseaseDisease
Known diseases associated with this structure: Autoimmune polyglandular disease, type I OMIM:[607358], Ciliary dyskinesia, primary, 6 OMIM:[607421], Sveinsson choreoretinal atrophy OMIM:[189967]
About this StructureAbout this Structure
1CQH is a Protein complex structure of sequences from Homo sapiens. Active as DNA-(apurinic or apyrimidinic site) lyase, with EC number 4.2.99.18 Full crystallographic information is available from OCA.
ReferenceReference
The solution structure of human thioredoxin complexed with its target from Ref-1 reveals peptide chain reversal., Qin J, Clore GM, Kennedy WP, Kuszewski J, Gronenborn AM, Structure. 1996 May 15;4(5):613-20. PMID:8736558
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