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* Residue conservation analysis
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PDB id:
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Oxidoreductase
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Title:
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Crystal structure of a complex between thioredoxin reductase, thioredoxin, and the NADP+ analog, aadp+
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Structure:
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Thioredoxin reductase. Chain: a, b, e, f. Engineered: yes. Mutation: yes. Thioredoxin 1. Chain: c, d, g, h. Engineered: yes. Mutation: yes
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Source:
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Escherichia coli. Organism_taxid: 562. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_taxid: 562
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Biol. unit:
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Octamer (from
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Resolution:
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2.95Å
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R-factor:
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0.205
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R-free:
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0.247
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Authors:
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B.W.Lennon,C.H.Williams Jr.,M.L.Ludwig
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Key ref:
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B.W.Lennon
et al.
(2000).
Twists in catalysis: alternating conformations of Escherichia coli thioredoxin reductase.
Science,
289,
1190-1194.
PubMed id:
DOI:
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Date:
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22-Jun-00
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Release date:
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30-Aug-00
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PROCHECK
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Headers
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References
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Enzyme class:
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Chains A, B, E, F:
E.C.1.8.1.9
- thioredoxin-disulfide reductase (NADPH).
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Reaction:
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[thioredoxin]-dithiol + NADP+ = [thioredoxin]-disulfide + NADPH + H+
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[thioredoxin]-dithiol
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+
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NADP(+)
Bound ligand (Het Group name = )
matches with 91.84% similarity
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=
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[thioredoxin]-disulfide
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+
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NADPH
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+
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H(+)
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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DOI no:
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Science
289:1190-1194
(2000)
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PubMed id:
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Twists in catalysis: alternating conformations of Escherichia coli thioredoxin reductase.
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B.W.Lennon,
C.H.Williams,
M.L.Ludwig.
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ABSTRACT
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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.
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Selected figure(s)
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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).
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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.
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The above figures are
reprinted
by permission from the AAAs:
Science
(2000,
289,
1190-1194)
copyright 2000.
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Figures were
selected
by an automated process.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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E.Karaca,
and
A.M.Bonvin
(2011).
A multidomain flexible docking approach to deal with large conformational changes in the modeling of biomolecular complexes.
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Structure,
19,
555-565.
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G.Hall,
and
J.Emsley
(2010).
Structure of human thioredoxin exhibits a large conformational change.
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Protein Sci,
19,
1807-1811.
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PDB code:
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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.
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Protein Sci,
19,
2279-2290.
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PDB codes:
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J.F.Collet,
and
J.Messens
(2010).
Structure, function, and mechanism of thioredoxin proteins.
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Antioxid Redox Signal,
13,
1205-1216.
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J.Obiero,
V.Pittet,
S.A.Bonderoff,
and
D.A.Sanders
(2010).
Thioredoxin system from Deinococcus radiodurans.
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J Bacteriol,
192,
494-501.
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PDB code:
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T.Y.Lin
(2010).
Protein-protein interaction as a powering source of oxidoreductive reactivity.
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Mol Biosyst,
6,
1454-1462.
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J.P.Jacquot,
H.Eklund,
N.Rouhier,
and
P.Schürmann
(2009).
Structural and evolutionary aspects of thioredoxin reductases in photosynthetic organisms.
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Trends Plant Sci,
14,
336-343.
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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.
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Acta Crystallogr D Biol Crystallogr,
65,
932-941.
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PDB code:
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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.
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Nat Struct Mol Biol,
16,
890-896.
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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.
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J Biol Chem,
284,
33305-33310.
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PDB code:
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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.
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Proc Natl Acad Sci U S A,
105,
6572-6577.
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PDB codes:
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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.
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Proteins,
70,
584-587.
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PDB code:
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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.
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J Mol Biol,
379,
520-534.
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PDB code:
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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.
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Proc Natl Acad Sci U S A,
104,
12276-12281.
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PDB codes:
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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.
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Neuroscience,
145,
1280-1299.
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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.
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Nature,
448,
92-96.
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PDB codes:
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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.
|
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Biochemistry,
46,
5709-5721.
|
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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.
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Acta Crystallogr D Biol Crystallogr,
63,
833-843.
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PDB codes:
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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.
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Proc Natl Acad Sci U S A,
103,
4410-4415.
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PDB code:
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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.
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Proc Natl Acad Sci U S A,
102,
15018-15023.
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PDB codes:
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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.
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Protein Sci,
14,
2195-2200.
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PDB code:
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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.
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Acta Crystallogr Sect F Struct Biol Cryst Commun,
61,
387-390.
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M.Akif,
K.Suhre,
C.Verma,
and
S.C.Mande
(2005).
Conformational flexibility of Mycobacterium tuberculosis thioredoxin reductase: crystal structure and normal-mode analysis.
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Acta Crystallogr D Biol Crystallogr,
61,
1603-1611.
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PDB code:
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E.Hitt,
and
M.L.Ludwig
(2004).
Biography of Martha L. Ludwig.
|
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Proc Natl Acad Sci U S A,
101,
3727-3728.
|
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E.Malito,
A.Alfieri,
M.W.Fraaije,
and
A.Mattevi
(2004).
Crystal structure of a Baeyer-Villiger monooxygenase.
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Proc Natl Acad Sci U S A,
101,
13157-13162.
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PDB code:
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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.
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Acta Crystallogr D Biol Crystallogr,
60,
1180-1184.
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PDB codes:
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M.Stehr,
and
Y.Lindqvist
(2004).
NrdH-redoxin of Corynebacterium ammoniagenes forms a domain-swapped dimer.
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Proteins,
55,
613-619.
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PDB code:
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N.M.Kamerbeek,
M.W.Fraaije,
and
D.B.Janssen
(2004).
Identifying determinants of NADPH specificity in Baeyer-Villiger monooxygenases.
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Eur J Biochem,
271,
2107-2116.
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S.Gromer,
S.Urig,
and
K.Becker
(2004).
The thioredoxin system--from science to clinic.
|
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Med Res Rev,
24,
40-89.
|
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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.
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Eur J Biochem,
271,
1437-1452.
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K.J.Woycechowsky,
and
R.T.Raines
(2003).
The CXC motif: a functional mimic of protein disulfide isomerase.
|
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Biochemistry,
42,
5387-5394.
|
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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.
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EMBO J,
20,
650-660.
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PDB codes:
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D.Ritz,
and
J.Beckwith
(2001).
Roles of thiol-redox pathways in bacteria.
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Annu Rev Microbiol,
55,
21-48.
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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.
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Nat Struct Biol,
8,
843-847.
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PDB codes:
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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.
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Protein Sci,
10,
2037-2049.
|
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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.
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Proc Natl Acad Sci U S A,
98,
9533-9538.
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PDB code:
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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.
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Biopolymers,
56,
1-7.
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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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