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PDBsum entry 1f6m
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Oxidoreductase
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PDB id
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1f6m
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Twists in catalysis: alternating conformations of escherichia coli thioredoxin reductase.
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Authors
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B.W.Lennon,
C.H.Williams,
M.L.Ludwig.
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Ref.
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Science, 2000,
289,
1190-1194.
[DOI no: ]
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PubMed id
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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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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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Secondary reference #1
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Title
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Crystal structure of escherichia coli thioredoxin reductase refined at 2 a resolution. Implications for a large conformational change during catalysis.
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Authors
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G.Waksman,
T.S.Krishna,
C.H.Williams,
J.Kuriyan.
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Ref.
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J Mol Biol, 1994,
236,
800-816.
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PubMed id
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Secondary reference #2
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Title
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Convergent evolution of similar function in two structurally divergent enzymes.
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Authors
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J.Kuriyan,
T.S.Krishna,
L.Wong,
B.Guenther,
A.Pahler,
C.H.Williams,
P.Model.
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Ref.
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Nature, 1991,
352,
172-174.
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PubMed id
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