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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_1ert|  PDB=1ert  | SIZE=300| SCENE=Thioredoxin/Cv/1 |right|CAPTION=Thioredoxin [[1ert]] }}


[[Thioredoxin]] (Trx) is an enzyme which facilitates the reduction of proteins by cysteine thiol-disulfide exchange.  They contain a CXXC motif. Trx-1 is a mammalian cellular protein.  Trx-2 is mitochondria-specific.  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. The images at the left and at the right correspond to one representative Trx, ''i.e.'' the crystal structure of human Thioredoxin ([[1ert]]).
== 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 />
* '''Trx-1''' is a mammalian cellular protein.<br />
* '''Trx-2''' is mitochondria-specific.<br />
* '''Trx C,M,X,Y''' are found in prokaryotes.<br />
*  '''Trx F,H,O''' are found in eukaryotes.<br />


{{TOC limit|limit=2}}


== 3D Structures of Thioredoxin ==
== Relevance ==
Serum Trx level is a predictor of steatohepatitis<ref>PMID:12480557</ref>.


== Disease ==
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>.


== 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>


=== Trx ===
== 3D Structures of Thioredoxin ==
 
[[Thioredoxin 3D structures]]
[[3e3e]], [[2hsh]], [[1aiu]], [[1erv]], [[1erw]] – hTrx (mutant) – human<br />
[[1cqg]], [[1cqh]] - hTrx (mutant)+Ref-1 peptide – NMR<br />
[[1mdi]], [[1mdj]], [[1mdk]] - hTrx + Target peptide of NFKB – NMR<br />
[[2hxk]], [[2ifq]], [[2iiy]] – hTrx S-nitroso<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 />
[[2k9f]] - Trx fragment+DsbD N-terminal – ''Neisseria meningitides'' – NMR<br />
[[3die]] – SaTrx (mutant) – ''Staphylococcus aureus''<br />
[[2voc]] - BsTrx (mutant) – ''Bacillus subtilis''<br />
[[2gzy]], [[2gzz]] – BsTrx – NMR<br />
[[2ipa]] – BsTrx (mutant)+ArcS (mutant) - NMR<br />
[[2h6x]], [[2trx]], [[1srx]] – EcTrx<br />
[[1xoa]], [[1xob]] – EcTrx - NMR<br />
[[1m7t]] – hTrx/EcTrx chimera - NMR<br />
[[3dxb]] – hTrx+Puf60 C-terminal<br />
[[3emx]] – Trx – ''Aeropyrum pernix''<br />
[[2vim]] – Trx – ''Fasciola hepatica''<br />
[[2yzu]], [[2cvk]], [[1v98]] – TtTrx – ''Thermus thermophilus''<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]] – Trx – ''Plasmodium falciparum''<br />
[[1r26]] – Trx – ''Trypanosoma brucei brucei''<br />
[[1gl8]] – Trx – spinach- NMR<br />
[[1fo5]] – Trx – ''Methanocaldococcus janaschii'' – NMR<br />
[[1quw]] – Trx – ''Bacillus acidocaldarius'' – NMR
 
 
=== Trx-1 ===
 
3f3q, 2i9h – yTrx-1 – yeast
3f3r – yTrx-1 (mutant)
3dyr, 2h6y, 2h6z, 2h70, 2h71, 2h72, 2h73, 2h74, 2h75, 2h76, 2fch, 2fd3, 1keb, 2eio, 2eiq, 2eir, 1zcp, 1zzy, 1txx, 1tho, 1tir  – EcTrx-1 (mutant) – Escherichia coli
1f6m – EcTrx-1+Trx reductase+AADP+
2ajq – EpTrx-1 (mutant)+DNA primer+DNA template+DNA polymerase – Enterobacteria phage T7
1zyq – EpTrx-1 (mutant)+DNA primer+DNA template+DNA polymerase+ATP
1x9m, 1x9s, 1x9w – EpTrx-1+DNA primer+DNA template+DNA polymerase+N-2-acetylaminofluorene-adducted DNA
1t8e – EpTrx-1 +DNA primer+DNA template+DNA polymerase+dCTP
1tk0 – EpTrx-1+DNA primer+DNA template+DNA polymerase+ddCTP+8-oxo-guanosine
1tk5 - EpTrx-1+DNA primer+DNA template+DNA polymerase+8-oxo-guanosine
1tk8 - EpTrx-1+DNA primer+DNA template+DNA polymerase+dAMP+8-oxo-guanosine
1tkd - EpTrx-1+DNA primer+DNA template+DNA polymerase+dCMP+8-oxo-guanosine
1skr - EpTrx-1+DNA primer+DNA template+DNA polymerase+ddATP
1sks, 1skw, 1sl0, 1sl1, 1sl2 - EpTrx-1+DNA primer+DNA template+DNA polymerase+thymine
1t7p - EpTrx-1+DNA primer+DNA template+DNA polymerase+ddAMP+ddGTP
2bto – Trx-1+tubulin btuba – prosthecobacter dejongeii
1oaz – Trx-1+immunoglobulin E – rat
 
 
=== Trx-2 ===
 
1w4v, 1w89, 1uvz – hTrx-2
3hhv – Trx-2 fragment – Sulfolobus solfataricus
2fa4 – yTrx-2
2ppt – Trx-2 – Rhodobacter capsulatus
2hsy – yTrx-2 - NMR
1thx – Trx-2 – Anabaena
 
 
=== Trx-3 ===
 
2oe0, 2oe1, 2oe3 – yTrx-3
 
 
=== Trx C ===
 
2i1u – Trx C – ''Mycobacterium tuberculosis''
 
=== Trx F ===
 
2pu9 – SsTrx F+ferredoxin thioredoxin reductase – Synechocystis
2pvo - SsTrx F+ferredoxin thioredoxin reductase+ferredoxin 1
1f9m – sTrx F – spinach
1faa - sTrx F (mutant)
 
 
=== Trx H ===
 
3d21 – pTrx H – poplar
3d22 - pTrx H (mutant)
1ti3 - pTrx H - NMR
2vlt, 2vlu, 2vlv, 2vm1, 2vm2 - bTrx H – barley
2iwt - bTrx H+alpha-amylase subtilisin inhibitor
1wmj – Trx H – Oryza sativa – NMR
1xfl – Trx H – Arabidopsis thaliana - NMR
1ep7 – CrTrx H – Chlamydomonas reinhardtii
1ep8 - CrTrx H (mutant)
1tof - CrTrx H - NMR
 


=== Trx M ===
</StructureSection>


2puk - SsTrx M+ferredoxin thioredoxin reductase
== References ==
1fb0, 1fb6 - sTrx M
<references/>
[[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