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PDBsum entry 2v6o
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Oxidoreductase
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PDB id
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2v6o
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References listed in PDB file
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Key reference
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Title
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Glutathione reductase and thioredoxin reductase at the crossroad: the structure of schistosoma mansoni thioredoxin glutathione reductase.
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Authors
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F.Angelucci,
A.E.Miele,
G.Boumis,
D.Dimastrogiovanni,
M.Brunori,
A.Bellelli.
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Ref.
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Proteins, 2008,
72,
936-945.
[DOI no: ]
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PubMed id
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Note In the PDB file this reference is
annotated as "TO BE PUBLISHED".
The citation details given above were identified by an automated
search of PubMed on title and author
names, giving a
perfect match.
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Abstract
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Thioredoxin glutathione reductase (TGR) is a key flavoenzyme expressed by
schistosomes that bridges two detoxification pathways crucial for the parasite
survival in the host's organism. In this article we report the crystal structure
(at 2.2 A resolution) of TGR from Schistosoma mansoni (SmTGR), deleted in the
last two residues. The structure reveals the peculiar architecture of this
chimeric enzyme: the small Glutaredoxin (Grx) domain at the N-terminus is joined
to the large thioredoxin reductase (TR) one via an extended complementary
surface, involving residues not conserved in the Grx superfamily; the TR domain
interacts with an identical partner via its C-terminal domain, forming a dimer
with a twisted "W" shape. Although lacking the penultimate Selenocysteine
residue (Sec), the enzyme is still able to reduce oxidized glutathione. These
data update the interpretation of the interdomain communication in TGR enzymes.
The possible function of this enzyme in pathogenic parasites is discussed.
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Figure 1.
Figure 1. The structure of truncated Schistosoma mansoni TGR in
ribbon representation, produced with CCP4MG.[23] Panel A:
Overall structural organization of the biological unit of the
enzyme: the W-shaped SmTGR dimer. One monomer is in blue and the
other monomer is colored according to the division in domains
from N- to C- terminus: Grx domain in light blue (1-107); FAD
binding domain in gold (108-257 and 391-461); NADPH binding
domain in green (258-358 and 364-390); the interface domain in
magenta (462-493). The linker regions between Grx and TR
(103-107) domains in magenta and the insertion (359-363)
peculiar to SmTGRs in red lie at the top and at the bottom,
respectively. Panel B: as in A, the view is from the top,
looking down the twofold dimerization axis (in black for
clarity). Panel C: The FAD binding site. View of the 2Fo-Fc
electron density map around the FAD cofactor contoured at 1.0
 .
The backbone of SmTGR around the active site is in ribbon, the
residues (K162 and Y296) that stabilize the position of the
flavine ring, together with the catalytic disulphide
(C154-C159), packing the isoalloxazine ring of the FAD, are
shown in sticks. Residues from the symmetrical monomer B, which
are implicated in the catalytic active site (H571B and E576B)
are also shown. Distances of the H-bond network range from 2.7
to 3.4 Å.
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Figure 2.
Figure 2. The putative orientation of NADPH and GSSG in SmTGR.
The SmTGR dimer is shown in a same orientation as in Figure
1(B), and is superimposed to hGR (olive-green) and hTR1 (grey).
For clarity the superimposition is displayed only for one
monomer. NADPH and GSSG from the superposed structures are
showed in CPK. Color coding as in Figure 1.
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The above figures are
reprinted
by permission from John Wiley & Sons, Inc.:
Proteins
(2008,
72,
936-945)
copyright 2008.
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