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[[Image:1ert.png|left|200px|thumb|Crystal Structure of Thioredoxin [[1ert]]]]
<StructureSection load='' size='350' side='right' caption='Human thioredoxin (PDB entry [[1ert]])' scene='43/430885/Cv/2'>
{{STRUCTURE_3kd0|  PDB=3kd0  | SIZE=400| SCENE= |right|CAPTION=Thioredoxin complex with Cd+2 (yellow) and Cl- (green) ions, [[3kd0]] }}


 
== Function ==
 
[[Thioredoxin]] (Trx) is an enzyme which facilitates, in its reduced form,  the reduction of proteins by cysteine thiol-disulfide exchange<ref>PMID:3152490</ref>.  They contain a CXXC motif.<br />
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[[Thioredoxin]] (Trx) is an enzyme which facilitates the reduction of proteins by cysteine thiol-disulfide exchange.  They contain a CXXC motif.<br />
* '''Trx-1''' is a mammalian cellular protein.<br />
* '''Trx-1''' is a mammalian cellular protein.<br />
*  '''Trx-2''' is mitochondria-specific.<br />
*  '''Trx-2''' is mitochondria-specific.<br />
In higher plants, Trx are divided to 6 groups based on their sequence. Trx M, X and Y are found in prokaryotes while F, H and O are found in eukaryotes.  
* '''Trx C,M,X,Y''' are found in prokaryotes.<br />
 
*  '''Trx F,H,O''' are found in eukaryotes.<br />
== 3D Structures of Thioredoxin ==


Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
{{#tree:id=OrganizedByTopic|openlevels=0|


*Thioredoxin
== Relevance ==
Serum Trx level is a predictor of steatohepatitis<ref>PMID:12480557</ref>.


**[[3e3e]], [[2hsh]], [[1aiu]], [[1erv]], [[1erw]], [[3m9j]], [[3m9k]], [[4oo4]] – hTrx (mutant) – human<br />
== Disease ==
**[[2hxk]], [[2ifq]], [[2iiy]] – hTrx S-nitroso<br />
Trx is involved in a wide range of human diseases and conditions including cancer, viral diseases, aging, cardiac conditions and more<ref>PMID:15990177</ref>.
**[[4oo5]] - hTrx S-nitroso (mutant)<br />
**[[1auc]], [[1ert]], [[1eru]], [[1trs]], [[1tru]], [[1trv]], [[1trw]], [[3trx]], [[4trx]] - hTrx<br />
**[[3hxs]] – BfTrx fragment – ''Bacteroides fragilis''<br />
**[[3hyp]] - BfrxI fragment (mutant)<br />
**[[3hz4]] – Trx – ''Methanosarcina mazei''<br />
**[[3die]] – SaTrx (mutant) – ''Staphylococcus aureus''<br />
**[[2voc]] - BsTrx (mutant) – ''Bacillus subtilis''<br />
**[[2gzy]], [[2gzz]] – BsTrx – NMR<br />
**[[2h6x]], [[2trx]], [[1srx]] – EcTrx<br />
**[[1xoa]], [[1xob]] – EcTrx - NMR<br />
**[[1m7t]] – hTrx/EcTrx chimera - NMR<br />
**[[3emx]] – Trx – ''Aeropyrum pernix''<br />
**[[2vim]] – Trx – ''Fasciola hepatica''<br />
**[[2yzu]], [[2cvk]], [[1v98]], [[4tn8]] – TtTrx – ''Thermus thermophilus''<br />
**[[2lst]] – TtTrx - NMR<br />
**[[2e0q]] – Trx (mutant) – ''Sulfolobus tokodaii''<br />
**[[2o7k]] – SaTrx<br />
**[[2o85]], [[2o87]], [[2o89]] – SaTrx (mutant)<br />
**[[2i4a]] – Trx – ''Acetobacter aceti''<br />
**[[2j23]] – Trx – ''Malassezia sympodialis''<br />
**[[2f51]] – Trx – ''Trichomonas vaginalis''<br />
**[[1t00]] – Trx – ''Streptomyces coelicolor''<br />
**[[1xw9]], [[1xwa]], [[1xwb]], [[1xwc]] – Trx – ''Drosophila melanogaster''<br />
**[[1rqm]], [[1nsw]], [[1nw2]] – Trx (mutant) – ''Alicyclobacillus acidocaldarius'' – NMR<br />
**[[1syr]] – PfTrx – ''Plasmodium falciparum''<br />
**[[2mmn]], [[2mmo]] - PfTrx - NMR<br />
**[[1r26]] – Trx – ''Trypanosoma brucei brucei''<br />
**[[1gl8]] – Trx – spinach - NMR<br />
**[[1fo5]] – Trx – ''Methanocaldococcus janaschii'' – NMR<br />
**[[1quw]] – Trx – ''Bacillus acidocaldarius'' – NMR<br />
**[[2l5l]] – Trx – ''Bacteroides vulgatus'' – NMR<br />
**[[2tir]], [[4hua]], [[4hu9]], [[4hu7]] - EcTrx (mutant) – ''Escherichia coli''<br />
**[[2xbi]] – SmTrx – ''Schistosoma mansoni''<br />
**[[2xbq]], [[2xc2]] – SmTrx (mutant)<br />
**[[4i8b]] - Trx – ''Schistosoma japonicum''<br />
**[[3zzx]], [[4aj8]], [[4aj7]], [[4aj6]], [[4v2l]], [[4v2m]], [[4v2n]] – Trx – ''Litopenaeus vannamei''<br />
**[[4fyu]] – Trx – ''Wuchereria bancrofti''<br />
**[[4knd]] – Trx – ''Anaeromyxobacter dehalogenans''<br />
**[[3vfi]] – Trx – Silicabacter phage dss3ϕ2<br />
**[[3zij]] – BcTrx – ''Bacillus cereus''<br />
**[[3zit]] - BcTrx (mutant)<br />
**[[2k8s]] – Trx – ''Nitrosomonas europaea'' - NMR<br />
**[[2l6c]], [[2l6d]] – Trx – ''Desulfovibrio vulgaris'' - NMR<br />
**[[2yj7]], [[2yn1]], [[2yoi]], [[2ypm]], [[3ziv]], [[4ba7]] – ancestral Trx – synthetic<br />
**[[4pob]] – Trx – ''Mycobacterium abscessus''<br />
**[[2ynx]], [[4ulx]] – Trx – Last Archaea Common Ancestor<br />
**[[4cw9]] - Trx (mutant) – ''Entamoeba histolytica''<br />
**[[4wxt]] - Trx – ''Mycobacterium avium''<br />


*Thioredoxin complexes
== Structural highlights ==
The <scene name='43/430885/Cv/4'>active site motif Cys-Gly-Pro-Cys</scene> is involved in the reduction of disulfide bonds in proteins<ref>PMID:8805557</ref>


**[[3kd0]] - hTrx (mutant)+CdCl2<br />
== 3D Structures of Thioredoxin ==
**[[4pok]], [[4pol]], [[4pom]] - hTrx (mutant)+ thioethanesulfonate<br />
[[Thioredoxin 3D structures]]
**[[4puf]] - hTrx (mutant)+ E3 ubiquitin-protein ligase<br />
**[[1cqg]], [[1cqh]] - hTrx (mutant)+Ref-1 peptide – NMR<br />
**[[1mdi]], [[1mdj]], [[1mdk]] - hTrx + Target peptide of NFKB – NMR<br />
**[[3dxb]] – hTrx+Puf60 C-terminal<br />
**[[2k9f]] - Trx fragment+DsbD N-terminal – ''Neisseria meningitides'' – NMR<br />
**[[2ipa]] – BsTrx (mutant)+ArcS (mutant) - NMR<br />
 
*Thioredoxin 1
 
**[[3f3q]], [[2i9h]] – yTrx-1 – yeast<br />
**[[3f3r]] – yTrx-1 (mutant)<br />
**[[3dyr]], [[2h6y]], [[2h6z]], [[2h70]], [[2h71]], [[2h72]], [[2h73]], [[2h74]], [[2h75]], [[2h76]], [[2fch]], [[2fd3]], [[1keb]], [[2eio]], [[2eiq]], [[2eir]], [[1zcp]], [[1zzy]], [[1txx]], [[1tho]] – EcTrx-1 (mutant) <br />
**[[1f6m]] – EcTrx-1+Trx reductase+AADP+<br />
**[[2o8v]] - EcTrx-1 (mutant) + PAPS reductase<br />
**[[2ajq]] – EpTrx-1 (mutant)+DNA primer+DNA template+DNA polymerase – Enterobacteria phage T7<br />
**[[1zyq]] – EpTrx-1 (mutant)+DNA primer+DNA template+DNA polymerase+ATP<br />
**[[1x9m]], [[1x9s]], [[1x9w]] – EpTrx-1+DNA primer+DNA template+DNA polymerase+N-2-acetylaminofluorene-adducted DNA<br />
**[[1t8e]] – EpTrx-1 +DNA primer+DNA template+DNA polymerase+dCTP<br />
**[[1tk0]] – EpTrx-1+DNA primer+DNA template+DNA polymerase+ddCTP+8-oxo-guanosine<br />
**[[1tk5]] - EpTrx-1+DNA primer+DNA template+DNA polymerase+8-oxo-guanosine<br />
**[[1tk8]] - EpTrx-1+DNA primer+DNA template+DNA polymerase+dAMP+8-oxo-guanosine<br />
**[[1tkd]] - EpTrx-1+DNA primer+DNA template+DNA polymerase+dCMP+8-oxo-guanosine<br />
**[[1skr]] - EpTrx-1+DNA primer+DNA template+DNA polymerase+ddATP<br />
**[[1sks]], [[1skw]], [[1sl0]], [[1sl1]], [[1sl2]] - EpTrx-1+DNA primer+DNA template+DNA polymerase+thymine<br />
**[[1t7p]] - EpTrx-1+DNA primer+DNA template+DNA polymerase+ddAMP+ddGTP<br />
**[[2bto]] – Trx-1+tubulin btuba – ''Prosthecobacter dejongeii''<br />
**[[1oaz]] – Trx-1+immunoglobulin E – rat<br />
**[[3tco]] - SsTrx-1 fragment – ''Sulfolobus solfataricus''<br />
**[[4j57]], [[4j56]] – PfTrx-1 + Trx reductase (mutant)<br />
**[[3zl5]] – SmTrx-1 (mutant)<br />
 
*Thioredoxin 2
 
**[[1w4v]], [[1w89]], [[1uvz]] – hTrx-2 <br />
**[[3hhv]] – SsTrx-2 fragment <br />
**[[2fa4]] – yTrx-2<br />
**[[2hsy]] – yTrx-2 - NMR<br />
**[[3pin]] - yTrx-2+peptide methionine sulfoxide reductase<br />
**[[4dss]] – yTrx-2 + peroxiredoxin-2<br />
**[[2ppt]] – Trx-2 – ''Rhodobacter capsulatus''<br />
**[[1thx]] – Trx-2 – Anabaena<br />
**[[3ul3]], [[4o32]] – PfTrx-2
 
*Thioredoxin 3
 
**[[2oe0]], [[2oe1]], [[2oe3]] – yTrx-3<br />
**[[4xhm]] – Trx-3 – ''Archaeoglobus fulgidus''<br />
 
*Thioredoxin C
 
**[[2i1u]] – MtTrx C – ''Mycobacterium tuberculosis''<br />
**[[2l4q]], [[2l59]] – MtTrx C - NMR<br />
**[[3nof]] – MtTrx (mutant)<br />
**[[3o6t]] – MtTrx (mutant)+quinol
 
*Thioredoxin F
 
**[[2pu9]] – SsTrx F+ferredoxin thioredoxin reductase – Synechocystis<br />
**[[2pvo]] - SsTrx F+ferredoxin thioredoxin reductase+ferredoxin 1<br />
**[[1f9m]] – sTrx F – spinach<br />
**[[1faa]] - sTrx F (mutant)
 
*Thioredoxin H
 
**[[3d21]] – pTrx H – poplar<br />
**[[3d22]] - pTrx H (mutant)<br />
**[[1ti3]] - pTrx H - NMR<br />
**[[2vlt]], [[2vlu]], [[2vlv]], [[2vm1]], [[2vm2]] - bTrx H – barley<br />
**[[2iwt]] - bTrx H+α-amylase subtilisin inhibitor<br />
**[[1wmj]] – Trx H – ''Oryza sativa'' – NMR<br />
**[[1xfl]] – Trx H – ''Arabidopsis thaliana'' - NMR<br />
**[[1ep7]] – CrTrx H – ''Chlamydomonas reinhardtii''<br />
**[[1ep8]] - CrTrx H (mutant)<br />
**[[1tof]] - CrTrx H - NMR


*Thioredoxin M
</StructureSection>


**[[2puk]] - SsTrx M+ferredoxin thioredoxin reductase<br />
== References ==
**[[1fb0]], [[1fb6]] - sTrx M<br />
<references/>
**[[1dby]] – CrTrx M – NMR<br />
}}
[[Category:Topic Page]]
[[Category:Topic Page]]

Latest revision as of 11:48, 23 February 2020


Function

Thioredoxin (Trx) is an enzyme which facilitates, in its reduced form, the reduction of proteins by cysteine thiol-disulfide exchange[1]. They contain a CXXC motif.

  • Trx-1 is a mammalian cellular protein.
  • Trx-2 is mitochondria-specific.
  • Trx C,M,X,Y are found in prokaryotes.
  • Trx F,H,O are found in eukaryotes.


Relevance

Serum Trx level is a predictor of steatohepatitis[2].

Disease

Trx is involved in a wide range of human diseases and conditions including cancer, viral diseases, aging, cardiac conditions and more[3].

Structural highlights

The is involved in the reduction of disulfide bonds in proteins[4]

3D Structures of Thioredoxin

Thioredoxin 3D structures


Human thioredoxin (PDB entry 1ert)

Drag the structure with the mouse to rotate

ReferencesReferences

  1. Gleason FK, Holmgren A. Thioredoxin and related proteins in procaryotes. FEMS Microbiol Rev. 1988 Dec;4(4):271-97. PMID:3152490
  2. Sumida Y, Nakashima T, Yoh T, Furutani M, Hirohama A, Kakisaka Y, Nakajima Y, Ishikawa H, Mitsuyoshi H, Okanoue T, Kashima K, Nakamura H, Yodoi J. Serum thioredoxin levels as a predictor of steatohepatitis in patients with nonalcoholic fatty liver disease. J Hepatol. 2003 Jan;38(1):32-8. PMID:12480557
  3. Burke-Gaffney A, Callister ME, Nakamura H. Thioredoxin: friend or foe in human disease? Trends Pharmacol Sci. 2005 Aug;26(8):398-404. PMID:15990177 doi:http://dx.doi.org/10.1016/j.tips.2005.06.005
  4. Weichsel A, Gasdaska JR, Powis G, Montfort WR. Crystal structures of reduced, oxidized, and mutated human thioredoxins: evidence for a regulatory homodimer. Structure. 1996 Jun 15;4(6):735-51. PMID:8805557

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Alexander Berchansky, Michal Harel, Joel L. Sussman