1qfn
From Proteopedia
(New page: 200px<br /><applet load="1qfn" size="450" color="white" frame="true" align="right" spinBox="true" caption="1qfn" /> '''GLUTAREDOXIN-1-RIBONUCLEOTIDE REDUCTASE B1 M...) |
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| - | [[Image:1qfn.jpg|left|200px]]<br /><applet load="1qfn" size=" | + | [[Image:1qfn.jpg|left|200px]]<br /><applet load="1qfn" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1qfn" /> | caption="1qfn" /> | ||
'''GLUTAREDOXIN-1-RIBONUCLEOTIDE REDUCTASE B1 MIXED DISULFIDE BOND'''<br /> | '''GLUTAREDOXIN-1-RIBONUCLEOTIDE REDUCTASE B1 MIXED DISULFIDE BOND'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The reduction equivalents necessary for the ribonucleotide reductase | + | The reduction equivalents necessary for the ribonucleotide reductase (RNR)-catalyzed production of deoxyribonucleotides are provided by glutaredoxin (Grx) or thioredoxin (Trx). The initial location for transfer of reducing equivalents to RNR is located at the C terminus of the B1 subunit and involves the reduction of a disulfide between Cys754 and Cys759. We have used a 25-mer peptide corresponding to residues 737-761 of RNR B1 (C754-->S) to synthesize a stable mixed disulfide with Escherichia coli Grx-1 (C14-->S) resembling the structure of an intermediate in the reaction. The high-resolution solution structure of the mixed disulfide has been obtained by NMR with an RMSD of 0.56 A for all the backbone atoms of the protein and the well-defined portion of the peptide. The binding interactions responsible for specificity have been identified demonstrating the importance of electrostatic interactions in this system and providing a rationale for the specificity of the Grx-RNR interaction. The disulfide is buried in this complex, implying a solely intra-molecular mechanism of reduction in contrast to the previously determined structure of the glutathione complex where the disulfide was exposed; mutagenesis studies have shown the relevance of intermolecular reduction processes. Substantial conformational changes in the helices of the protein are associated with peptide binding which have significant mechanistic implications for protein disulfide reduction by glutaredoxins. |
==About this Structure== | ==About this Structure== | ||
| - | 1QFN is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Active as [http://en.wikipedia.org/wiki/Ribonucleoside-diphosphate_reductase Ribonucleoside-diphosphate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.17.4.1 1.17.4.1] Full crystallographic information is available from [http:// | + | 1QFN is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Active as [http://en.wikipedia.org/wiki/Ribonucleoside-diphosphate_reductase Ribonucleoside-diphosphate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.17.4.1 1.17.4.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QFN OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Ribonucleoside-diphosphate reductase]] | [[Category: Ribonucleoside-diphosphate reductase]] | ||
| - | [[Category: Berardi, M | + | [[Category: Berardi, M J.]] |
| - | [[Category: Bushweller, J | + | [[Category: Bushweller, J H.]] |
[[Category: disulfide]] | [[Category: disulfide]] | ||
[[Category: electron transfer]] | [[Category: electron transfer]] | ||
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[[Category: ribonucleotide reductase]] | [[Category: ribonucleotide reductase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:39:00 2008'' |
Revision as of 12:39, 21 February 2008
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GLUTAREDOXIN-1-RIBONUCLEOTIDE REDUCTASE B1 MIXED DISULFIDE BOND
Overview
The reduction equivalents necessary for the ribonucleotide reductase (RNR)-catalyzed production of deoxyribonucleotides are provided by glutaredoxin (Grx) or thioredoxin (Trx). The initial location for transfer of reducing equivalents to RNR is located at the C terminus of the B1 subunit and involves the reduction of a disulfide between Cys754 and Cys759. We have used a 25-mer peptide corresponding to residues 737-761 of RNR B1 (C754-->S) to synthesize a stable mixed disulfide with Escherichia coli Grx-1 (C14-->S) resembling the structure of an intermediate in the reaction. The high-resolution solution structure of the mixed disulfide has been obtained by NMR with an RMSD of 0.56 A for all the backbone atoms of the protein and the well-defined portion of the peptide. The binding interactions responsible for specificity have been identified demonstrating the importance of electrostatic interactions in this system and providing a rationale for the specificity of the Grx-RNR interaction. The disulfide is buried in this complex, implying a solely intra-molecular mechanism of reduction in contrast to the previously determined structure of the glutathione complex where the disulfide was exposed; mutagenesis studies have shown the relevance of intermolecular reduction processes. Substantial conformational changes in the helices of the protein are associated with peptide binding which have significant mechanistic implications for protein disulfide reduction by glutaredoxins.
About this Structure
1QFN is a Protein complex structure of sequences from Escherichia coli. Active as Ribonucleoside-diphosphate reductase, with EC number 1.17.4.1 Full crystallographic information is available from OCA.
Reference
Binding specificity and mechanistic insight into glutaredoxin-catalyzed protein disulfide reduction., Berardi MJ, Bushweller JH, J Mol Biol. 1999 Sep 10;292(1):151-61. PMID:10493864
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