2hsh
From Proteopedia
(New page: 200px<br /> <applet load="2hsh" size="450" color="white" frame="true" align="right" spinBox="true" caption="2hsh, resolution 1.35Å" /> '''Crystal structure o...) |
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| - | [[Image:2hsh.gif|left|200px]]<br /> | + | [[Image:2hsh.gif|left|200px]]<br /><applet load="2hsh" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2hsh" size=" | + | |
caption="2hsh, resolution 1.35Å" /> | caption="2hsh, resolution 1.35Å" /> | ||
'''Crystal structure of C73S mutant of human thioredoxin-1 oxidized with H2O2'''<br /> | '''Crystal structure of C73S mutant of human thioredoxin-1 oxidized with H2O2'''<br /> | ||
==Overview== | ==Overview== | ||
| - | We have determined the 1.65 A crystal structure of human thioredoxin-1 | + | We have determined the 1.65 A crystal structure of human thioredoxin-1 after treatment with S-nitrosoglutathione, providing a high-resolution view of this important protein modification and mechanistic insight into protein transnitrosation. Thioredoxin-1 appears to play an intermediary role in cellular S-nitrosylation and is important in numerous biological and pathobiological activities. S-Nitroso modifications of cysteines 62 and 69 are clearly visible in the structure and display planar cis geometries, whereas cysteines 32, 35, and 73 form intra- and intermolecular disulfide bonds. Surprisingly, the Cys 62 nitroso group is completely buried and pointing to the protein interior yet is the most readily formed at neutral pH. The Cys 69 nitroso group is also protected but requires a higher pH for stable formation. The helix intervening between residues 62 and 69 shifts by approximately 0.5 A to accommodate the SNO groups. The crystallographic asymmetric unit contains three independent molecules of thioredoxin, providing three views of the nitrosated protein. The three molecules are in general agreement but display subtle differences, including both cis and trans conformers for Cys 69 SNO in molecule C, and greater disorder in the Cys 62-Cys 69 helix in molecule B. Possible mechanisms for protein transnitrosation with specific geometric requirements and charge stabilization of the nitroxyl disulfide reaction intermediate are discussed. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2HSH is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with PO4 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 2HSH is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=PO4:'>PO4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HSH OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Montfort, W | + | [[Category: Montfort, W R.]] |
[[Category: Weichsel, A.]] | [[Category: Weichsel, A.]] | ||
[[Category: PO4]] | [[Category: PO4]] | ||
[[Category: mutant]] | [[Category: mutant]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:45:14 2008'' |
Revision as of 15:45, 21 February 2008
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Crystal structure of C73S mutant of human thioredoxin-1 oxidized with H2O2
Contents |
Overview
We have determined the 1.65 A crystal structure of human thioredoxin-1 after treatment with S-nitrosoglutathione, providing a high-resolution view of this important protein modification and mechanistic insight into protein transnitrosation. Thioredoxin-1 appears to play an intermediary role in cellular S-nitrosylation and is important in numerous biological and pathobiological activities. S-Nitroso modifications of cysteines 62 and 69 are clearly visible in the structure and display planar cis geometries, whereas cysteines 32, 35, and 73 form intra- and intermolecular disulfide bonds. Surprisingly, the Cys 62 nitroso group is completely buried and pointing to the protein interior yet is the most readily formed at neutral pH. The Cys 69 nitroso group is also protected but requires a higher pH for stable formation. The helix intervening between residues 62 and 69 shifts by approximately 0.5 A to accommodate the SNO groups. The crystallographic asymmetric unit contains three independent molecules of thioredoxin, providing three views of the nitrosated protein. The three molecules are in general agreement but display subtle differences, including both cis and trans conformers for Cys 69 SNO in molecule C, and greater disorder in the Cys 62-Cys 69 helix in molecule B. Possible mechanisms for protein transnitrosation with specific geometric requirements and charge stabilization of the nitroxyl disulfide reaction intermediate are discussed.
Disease
Known disease associated with this structure: Ciliary dyskinesia, primary, 6 OMIM:[607421]
About this Structure
2HSH is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
Reference
Buried S-nitrosocysteine revealed in crystal structures of human thioredoxin., Weichsel A, Brailey JL, Montfort WR, Biochemistry. 2007 Feb 6;46(5):1219-27. PMID:17260951
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