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PDBsum entry 1f6m

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protein ligands Protein-protein interface(s) links
Oxidoreductase PDB id
1f6m
Jmol PyMol
Contents
Protein chains
320 a.a. *
108 a.a. *
Ligands
FAD ×4
3AA ×4
Waters ×236
* Residue conservation analysis
PDB id:
1f6m
Name: Oxidoreductase
Title: Crystal structure of a complex between thioredoxin reductase, thioredoxin, and the NADP+ analog, aadp+
Structure: Thioredoxin reductase. Chain: a, b, e, f. Engineered: yes. Mutation: yes. Thioredoxin 1. Chain: c, d, g, h. Engineered: yes. Mutation: yes
Source: Escherichia coli. Organism_taxid: 562. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_taxid: 562
Biol. unit: Octamer (from PQS)
Resolution:
2.95Å     R-factor:   0.205     R-free:   0.247
Authors: B.W.Lennon,C.H.Williams Jr.,M.L.Ludwig
Key ref:
B.W.Lennon et al. (2000). Twists in catalysis: alternating conformations of Escherichia coli thioredoxin reductase. Science, 289, 1190-1194. PubMed id: 10947986 DOI: 10.1126/science.289.5482.1190
Date:
22-Jun-00     Release date:   30-Aug-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P0A9P4  (TRXB_ECOLI) -  Thioredoxin reductase
Seq:
Struc:
321 a.a.
320 a.a.*
Protein chains
Pfam   ArchSchema ?
P0AA25  (THIO_ECOLI) -  Thioredoxin 1
Seq:
Struc:
109 a.a.
108 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chains A, B, E, F: E.C.1.8.1.9  - Thioredoxin-disulfide reductase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Thioredoxin + NADP+ = thioredoxin disulfide + NADPH
Thioredoxin
+
NADP(+)
Bound ligand (Het Group name = 3AA)
matches with 91.00% similarity
= thioredoxin disulfide
+ NADPH
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   2 terms 
  Biological process     viral reproduction   7 terms 
  Biochemical function     protein binding     7 terms  

 

 
    reference    
 
 
DOI no: 10.1126/science.289.5482.1190 Science 289:1190-1194 (2000)
PubMed id: 10947986  
 
 
Twists in catalysis: alternating conformations of Escherichia coli thioredoxin reductase.
B.W.Lennon, C.H.Williams, M.L.Ludwig.
 
  ABSTRACT  
 
In thioredoxin reductase (TrxR) from Escherichia coli, cycles of reduction and reoxidation of the flavin adenine dinucleotide (FAD) cofactor depend on rate-limiting rearrangements of the FAD and NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) domains. We describe the structure of the flavin-reducing conformation of E. coli TrxR at a resolution of 3.0 angstroms. The orientation of the two domains permits reduction of FAD by NADPH and oxidation of the enzyme dithiol by the protein substrate, thioredoxin. The alternate conformation, described by Kuriyan and co-workers, permits internal transfer of reducing equivalents from reduced FAD to the active-site disulfide. Comparison of these structures demonstrates that switching between the two conformations involves a "ball-and-socket" motion in which the pyridine nucleotide-binding domain rotates by 67 degrees.
 
  Selected figure(s)  
 
Figure 1.
Fig. 1. Reaction catalyzed by thioredoxin reductase. Reducing equivalents from NADPH are transferred to the flavin cofactor, then to the enzyme disulfide (Cys135-Cys138), and finally to the disulfide (Cys32-Cys35) of the substrate, oxidized thioredoxin (30). Reduced thioredoxin is a reductant for ribonucleotide reductase and an activator of T7 DNA polymerase (31, 32).
Figure 3.
Fig. 3. The dimer of the TrxR-Trx complex with TrxR in the FR conformation, viewed down the molecular dyad. Blue and cyan denote one monomer of the TrxR dimer; gold and yellow denote the second monomer. The TrxR-Trx protomer on the right is designated A; the protomer on the left is B. These are related to protomers C and D, respectively, by NCS. Each NADPH domain contacts both of the FAD domains of the dimer. The thioredoxin substrates (gray), which bind and react at opposite ends of the TrxR dimer, are accommodated by the FR conformation. FAD, AADP+, and the TrxR-thioredoxin cross-link (sulfurs in green) are drawn in ball-and-stick mode.
 
  The above figures are reprinted by permission from the AAAs: Science (2000, 289, 1190-1194) copyright 2000.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21481778 E.Karaca, and A.M.Bonvin (2011).
A multidomain flexible docking approach to deal with large conformational changes in the modeling of biomolecular complexes.
  Structure, 19, 555-565.  
20661909 G.Hall, and J.Emsley (2010).
Structure of human thioredoxin exhibits a large conformational change.
  Protein Sci, 19, 1807-1811.
PDB code: 3e3e
20878669 H.Komori, D.Seo, T.Sakurai, and Y.Higuchi (2010).
Crystal structure analysis of Bacillus subtilis ferredoxin-NADP(+) oxidoreductase and the structural basis for its substrate selectivity.
  Protein Sci, 19, 2279-2290.
PDB codes: 3lzw 3lzx
20136512 J.F.Collet, and J.Messens (2010).
Structure, function, and mechanism of thioredoxin proteins.
  Antioxid Redox Signal, 13, 1205-1216.  
19933368 J.Obiero, V.Pittet, S.A.Bonderoff, and D.A.Sanders (2010).
Thioredoxin system from Deinococcus radiodurans.
  J Bacteriol, 192, 494-501.
PDB code: 2q7v
20473443 T.Y.Lin (2010).
Protein-protein interaction as a powering source of oxidoreductive reactivity.
  Mol Biosyst, 6, 1454-1462.  
19446492 J.P.Jacquot, H.Eklund, N.Rouhier, and P.Schürmann (2009).
Structural and evolutionary aspects of thioredoxin reductases in photosynthetic organisms.
  Trends Plant Sci, 14, 336-343.  
19690371 K.G.Kirkensgaard, P.Hägglund, C.Finnie, B.Svensson, and A.Henriksen (2009).
Structure of Hordeum vulgare NADPH-dependent thioredoxin reductase 2. Unwinding the reaction mechanism.
  Acta Crystallogr D Biol Crystallogr, 65, 932-941.
PDB code: 2whd
19597482 R.Perez-Jimenez, J.Li, P.Kosuri, I.Sanchez-Romero, A.P.Wiita, D.Rodriguez-Larrea, A.Chueca, A.Holmgren, A.Miranda-Vizuete, K.Becker, S.H.Cho, J.Beckwith, E.Gelhaye, J.P.Jacquot, E.Gaucher, J.M.Sanchez-Ruiz, B.J.Berne, and J.M.Fernandez (2009).
Diversity of chemical mechanisms in thioredoxin catalysis revealed by single-molecule force spectroscopy.
  Nat Struct Mol Biol, 16, 890-896.  
19812042 T.J.Jönsson, L.C.Johnson, and W.T.Lowther (2009).
Protein engineering of the quaternary sulfiredoxin.peroxiredoxin enzyme.substrate complex reveals the molecular basis for cysteine sulfinic acid phosphorylation.
  J Biol Chem, 284, 33305-33310.
PDB code: 3hy2
18443301 A.Alfieri, E.Malito, R.Orru, M.W.Fraaije, and A.Mattevi (2008).
Revealing the moonlighting role of NADP in the structure of a flavin-containing monooxygenase.
  Proc Natl Acad Sci U S A, 105, 6572-6577.
PDB codes: 2vq7 2vqb
17932921 A.S.Pinheiro, G.C.Amorim, L.E.Netto, F.C.Almeida, and A.P.Valente (2008).
NMR solution structure of the reduced form of thioredoxin 1 from Sacharomyces cerevisiae.
  Proteins, 70, 584-587.
PDB code: 2i9h
18455736 T.R.Kouwen, J.Andréll, R.Schrijver, J.Y.Dubois, M.J.Maher, S.Iwata, E.P.Carpenter, and J.M.van Dijl (2008).
Thioredoxin A active-site mutants form mixed disulfide dimers that resemble enzyme-substrate reaction intermediates.
  J Mol Biol, 379, 520-534.
PDB code: 2voc
17636129 G.Hagelueken, L.Wiehlmann, T.M.Adams, H.Kolmar, D.W.Heinz, B.Tümmler, and W.D.Schubert (2007).
Crystal structure of the electron transfer complex rubredoxin rubredoxin reductase of Pseudomonas aeruginosa.
  Proc Natl Acad Sci U S A, 104, 12276-12281.
PDB codes: 2v3a 2v3b
17174478 J.J.Perry, L.Fan, and J.A.Tainer (2007).
Developing master keys to brain pathology, cancer and aging from the structural biology of proteins controlling reactive oxygen species and DNA repair.
  Neuroscience, 145, 1280-1299.  
17611542 S.Dai, R.Friemann, D.A.Glauser, F.Bourquin, W.Manieri, P.Schürmann, and H.Eklund (2007).
Structural snapshots along the reaction pathway of ferredoxin-thioredoxin reductase.
  Nature, 448, 92-96.
PDB codes: 2pu9 2puk 2puo 2pvd 2pvg 2pvo
17441733 T.J.Jönsson, H.R.Ellis, and L.B.Poole (2007).
Cysteine reactivity and thiol-disulfide interchange pathways in AhpF and AhpC of the bacterial alkyl hydroperoxide reductase system.
  Biochemistry, 46, 5709-5721.  
17582174 T.N.Gustafsson, T.Sandalova, J.Lu, A.Holmgren, and G.Schneider (2007).
High-resolution structures of oxidized and reduced thioredoxin reductase from Helicobacter pylori.
  Acta Crystallogr D Biol Crystallogr, 63, 833-843.
PDB codes: 2q0k 2q0l
16537372 C.L.Colbert, Q.Wu, P.J.Erbel, K.H.Gardner, and J.Deisenhofer (2006).
Mechanism of substrate specificity in Bacillus subtilis ResA, a thioredoxin-like protein involved in cytochrome c maturation.
  Proc Natl Acad Sci U S A, 103, 4410-4415.
PDB code: 2f9s
16217027 E.I.Biterova, A.A.Turanov, V.N.Gladyshev, and J.J.Barycki (2005).
Crystal structures of oxidized and reduced mitochondrial thioredoxin reductase provide molecular details of the reaction mechanism.
  Proc Natl Acad Sci U S A, 102, 15018-15023.
PDB codes: 1zdl 1zkq
15987893 F.C.Peterson, B.L.Lytle, S.Sampath, D.Vinarov, E.Tyler, M.Shahan, J.L.Markley, and B.F.Volkman (2005).
Solution structure of thioredoxin h1 from Arabidopsis thaliana.
  Protein Sci, 14, 2195-2200.
PDB code: 1xfl
  16511049 M.A.Oliveira, K.F.Discola, S.V.Alves, J.A.Barbosa, F.J.Medrano, L.E.Netto, and B.G.Guimarães (2005).
Crystallization and preliminary X-ray diffraction analysis of NADPH-dependent thioredoxin reductase I from Saccharomyces cerevisiae.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 61, 387-390.  
16301794 M.Akif, K.Suhre, C.Verma, and S.C.Mande (2005).
Conformational flexibility of Mycobacterium tuberculosis thioredoxin reductase: crystal structure and normal-mode analysis.
  Acta Crystallogr D Biol Crystallogr, 61, 1603-1611.
PDB code: 2a87
15010540 E.Hitt, and M.L.Ludwig (2004).
Biography of Martha L. Ludwig.
  Proc Natl Acad Sci U S A, 101, 3727-3728.  
15328411 E.Malito, A.Alfieri, M.W.Fraaije, and A.Mattevi (2004).
Crystal structure of a Baeyer-Villiger monooxygenase.
  Proc Natl Acad Sci U S A, 101, 13157-13162.
PDB code: 1w4x
15159594 J.Messens, I.Van Molle, P.Vanhaesebrouck, K.Van Belle, K.Wahni, J.C.Martins, L.Wyns, and R.Loris (2004).
The structure of a triple mutant of pI258 arsenate reductase from Staphylococcus aureus and its 5-thio-2-nitrobenzoic acid adduct.
  Acta Crystallogr D Biol Crystallogr, 60, 1180-1184.
PDB codes: 1rxe 1rxi
15103625 M.Stehr, and Y.Lindqvist (2004).
NrdH-redoxin of Corynebacterium ammoniagenes forms a domain-swapped dimer.
  Proteins, 55, 613-619.
PDB code: 1r7h
15153101 N.M.Kamerbeek, M.W.Fraaije, and D.B.Janssen (2004).
Identifying determinants of NADPH specificity in Baeyer-Villiger monooxygenases.
  Eur J Biochem, 271, 2107-2116.  
14595672 S.Gromer, S.Urig, and K.Becker (2004).
The thioredoxin system--from science to clinic.
  Med Res Rev, 24, 40-89.  
15066170 W.Eisenreich, K.Kemter, A.Bacher, S.B.Mulrooney, C.H.Williams, and F.Müller (2004).
13C-, 15N- and 31P-NMR studies of oxidized and reduced low molecular mass thioredoxin reductase and some mutant proteins.
  Eur J Biochem, 271, 1437-1452.  
12731880 K.J.Woycechowsky, and R.T.Raines (2003).
The CXC motif: a functional mimic of protein disulfide isomerase.
  Biochemistry, 42, 5387-5394.  
11179210 D.Dobritzsch, G.Schneider, K.D.Schnackerz, and Y.Lindqvist (2001).
Crystal structure of dihydropyrimidine dehydrogenase, a major determinant of the pharmacokinetics of the anti-cancer drug 5-fluorouracil.
  EMBO J, 20, 650-660.
PDB codes: 1h7w 1h7x
11544348 D.Ritz, and J.Beckwith (2001).
Roles of thiol-redox pathways in bacteria.
  Annu Rev Microbiol, 55, 21-48.  
11573087 I.Zegers, J.C.Martins, R.Willem, L.Wyns, and J.Messens (2001).
Arsenate reductase from S. aureus plasmid pI258 is a phosphatase drafted for redox duty.
  Nat Struct Biol, 8, 843-847.
PDB codes: 1jf8 1jfv
11567095 P.A.van den Berg, S.B.Mulrooney, B.Gobets, I.H.van Stokkum, A.van Hoek, C.H.Williams, and A.J.Visser (2001).
Exploring the conformational equilibrium of E. coli thioredoxin reductase: characterization of two catalytically important states by ultrafast flavin fluorescence spectroscopy.
  Protein Sci, 10, 2037-2049.  
11481439 T.Sandalova, L.Zhong, Y.Lindqvist, A.Holmgren, and G.Schneider (2001).
Three-dimensional structure of a mammalian thioredoxin reductase: implications for mechanism and evolution of a selenocysteine-dependent enzyme.
  Proc Natl Acad Sci U S A, 98, 9533-9538.
PDB code: 1h6v
11582571 V.Menchise, C.Corbier, C.Didierjean, J.P.Jacquot, E.Benedetti, M.Saviano, and A.Aubry (2000).
Crystal structure of the W35A mutant thioredoxin h from Chlamydomonas reinhardtii: the substitution of the conserved active site Trp leads to modifications in the environment of the two catalytic cysteines.
  Biopolymers, 56, 1-7.  
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 code is shown on the right.

 

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