View source for 2hsh


==Crystal structure of C73S mutant of human thioredoxin-1 oxidized with H2O2==
<StructureSection load='2hsh' size='340' side='right'caption='[[2hsh]], [[Resolution|resolution]] 1.35&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2hsh]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HSH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HSH FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.35&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2hsh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hsh OCA], [https://pdbe.org/2hsh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hsh RCSB], [https://www.ebi.ac.uk/pdbsum/2hsh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hsh ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/THIO_HUMAN THIO_HUMAN] Participates in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide and catalyzes dithiol-disulfide exchange reactions. Plays a role in the reversible S-nitrosylation of cysteine residues in target proteins, and thereby contributes to the response to intracellular nitric oxide. Nitrosylates the active site Cys of CASP3 in response to nitric oxide (NO), and thereby inhibits caspase-3 activity. Induces the FOS/JUN AP-1 DNA-binding activity in ionizing radiation (IR) cells through its oxidation/reduction status and stimulates AP-1 transcriptional activity.<ref>PMID:2176490</ref> <ref>PMID:9108029</ref> <ref>PMID:11118054</ref> <ref>PMID:16408020</ref> <ref>PMID:17606900</ref>   ADF augments the expression of the interleukin-2 receptor TAC (IL2R/P55).<ref>PMID:2176490</ref> <ref>PMID:9108029</ref> <ref>PMID:11118054</ref> <ref>PMID:16408020</ref> <ref>PMID:17606900</ref> 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hs/2hsh_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2hsh ConSurf].
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== Publication Abstract from PubMed ==
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.

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<ref>PMID:17260951</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2hsh" style="background-color:#fffaf0;"></div>

==See Also==
*[[Thioredoxin 3D structures|Thioredoxin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Montfort WR]]
[[Category: Weichsel A]]