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PDBsum entry 2hsh
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Oxidoreductase PDB id
2hsh

 

 

 

 

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Contents
Protein chain
105 a.a. *
Ligands
PO4
Waters ×133
* Residue conservation analysis
PDB id:
2hsh
Name: Oxidoreductase
Title: Crystal structure of c73s mutant of human thioredoxin-1 oxidized with h2o2
Structure: Thioredoxin. Chain: a. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: txn. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
Resolution:
1.35Å     R-factor:   0.125     R-free:   0.168
Authors: A.Weichsel,W.R.Montfort
Key ref: A.Weichsel et al. (2007). Buried S-nitrosocysteine revealed in crystal structures of human thioredoxin. Biochemistry, 46, 1219-1227. PubMed id: 17260951 DOI: 10.1021/bi061878r
Date:
21-Jul-06     Release date:   05-Dec-06    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P10599  (THIO_HUMAN) -  Thioredoxin from Homo sapiens
Seq:
Struc: 		105 a.a.
105 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 

 
DOI no: 10.1021/bi061878r Biochemistry 46:1219-1227 (2007)
PubMed id: 17260951  
 
 
Buried S-nitrosocysteine revealed in crystal structures of human thioredoxin.
A.Weichsel, J.L.Brailey, W.R.Montfort.
 
  ABSTRACT  
 
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.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20662007 A.Weichsel, M.Kem, and W.R.Montfort (2010).
Crystal structure of human thioredoxin revealing an unraveled helix and exposed S-nitrosation site.
  Protein Sci, 19, 1801-1806.
PDB codes: 3m9j 3m9k
20660346 C.Wu, T.Liu, W.Chen, S.Oka, C.Fu, M.R.Jain, A.M.Parrott, A.T.Baykal, J.Sadoshima, and H.Li (2010).
Redox regulatory mechanism of transnitrosylation by thioredoxin.
  Mol Cell Proteomics, 9, 2262-2275.  
19738628 M.Benhar, M.T.Forrester, and J.S.Stamler (2009).
Protein denitrosylation: enzymatic mechanisms and cellular functions.
  Nat Rev Mol Cell Biol, 10, 721-732.  
19864628 M.W.Foster, M.T.Forrester, and J.S.Stamler (2009).
A protein microarray-based analysis of S-nitrosylation.
  Proc Natl Acad Sci U S A, 106, 18948-18953.  
19101475 J.S.Paige, G.Xu, B.Stancevic, and S.R.Jaffrey (2008).
Nitrosothiol reactivity profiling identifies S-nitrosylated proteins with unexpected stability.
  Chem Biol, 15, 1307-1316.  
18544525 S.I.Hashemy, and A.Holmgren (2008).
Regulation of the catalytic activity and structure of human thioredoxin 1 via oxidation and S-nitrosylation of cysteine residues.
  J Biol Chem, 283, 21890-21898.  
18323623 T.Karlberg, R.Collins, S.van den Berg, A.Flores, M.Hammarström, M.Högbom, L.Holmberg Schiavone, and J.Uppenberg (2008).
Structure of human argininosuccinate synthetase.
  Acta Crystallogr D Biol Crystallogr, 64, 279-286.
PDB code: 2nz2
18515359 X.Hu, L.B.Murata, A.Weichsel, J.L.Brailey, S.A.Roberts, A.Nighorn, and W.R.Montfort (2008).
Allostery in recombinant soluble guanylyl cyclase from Manduca sexta.
  J Biol Chem, 283, 20968-20977.  
18635375 Y.Wang, T.Liu, C.Wu, and H.Li (2008).
A strategy for direct identification of protein S-nitrosylation sites by quadrupole time-of-flight mass spectrometry.
  J Am Soc Mass Spectrom, 19, 1353-1360.  
17606900 D.A.Mitchell, S.U.Morton, N.B.Fernhoff, and M.A.Marletta (2007).
Thioredoxin is required for S-nitrosation of procaspase-3 and the inhibition of apoptosis in Jurkat cells.
  Proc Natl Acad Sci U S A, 104, 11609-11614.  
17488722 E.R.Schreiter, M.M.Rodríguez, A.Weichsel, W.R.Montfort, and J.Bonaventura (2007).
S-nitrosylation-induced conformational change in blackfin tuna myoglobin.
  J Biol Chem, 282, 19773-19780.
PDB codes: 2nrl 2nrm 2nx0
17636120 N.Sayed, P.Baskaran, X.Ma, F.van den Akker, and A.Beuve (2007).
Desensitization of soluble guanylyl cyclase, the NO receptor, by S-nitrosylation.
  Proc Natl Acad Sci U S A, 104, 12312-12317.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.

 

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