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PDBsum entry 2hsh
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Oxidoreductase
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PDB id
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2hsh
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References listed in PDB file
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Key reference
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Title
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Buried s-Nitrosocysteine revealed in crystal structures of human thioredoxin.
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Authors
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A.Weichsel,
J.L.Brailey,
W.R.Montfort.
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Ref.
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Biochemistry, 2007,
46,
1219-1227.
[DOI no: ]
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PubMed id
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Abstract
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We have determined the 1.65 A crystal structure of human thioredoxin-1 after
treatment with S-nitrosoglutathione, providing a high-resolution view of this
important protein modification and mechanistic insight into protein
transnitrosation. Thioredoxin-1 appears to play an intermediary role in cellular
S-nitrosylation and is important in numerous biological and pathobiological
activities. S-Nitroso modifications of cysteines 62 and 69 are clearly visible
in the structure and display planar cis geometries, whereas cysteines 32, 35,
and 73 form intra- and intermolecular disulfide bonds. Surprisingly, the Cys 62
nitroso group is completely buried and pointing to the protein interior yet is
the most readily formed at neutral pH. The Cys 69 nitroso group is also
protected but requires a higher pH for stable formation. The helix intervening
between residues 62 and 69 shifts by approximately 0.5 A to accommodate the SNO
groups. The crystallographic asymmetric unit contains three independent
molecules of thioredoxin, providing three views of the nitrosated protein. The
three molecules are in general agreement but display subtle differences,
including both cis and trans conformers for Cys 69 SNO in molecule C, and
greater disorder in the Cys 62-Cys 69 helix in molecule B. Possible mechanisms
for protein transnitrosation with specific geometric requirements and charge
stabilization of the nitroxyl disulfide reaction intermediate are discussed.
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Secondary reference #1
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Title
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Crystal structures of reduced, Oxidized, And mutated human thioredoxins: evidence for a regulatory homodimer.
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Authors
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A.Weichsel,
J.R.Gasdaska,
G.Powis,
W.R.Montfort.
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Ref.
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Structure, 1996,
4,
735-751.
[DOI no: ]
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PubMed id
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Figure 2.
Figure 2. Stereoviews of electron density for Cys73 and Ser73.
(a) 2F[o]–F[c] electron density map for the C73–C73′
disulfide bond in Trx-red (contoured at 1.0σ above the mean
value for the map). (b) Difference electron density map between
Trx-red and C73S for residue 73. Only positive electron density
is shown (contoured at 2.7σ). Figure 2. Stereoviews of
electron density for Cys73 and Ser73. (a) 2F[o]–F[c] electron
density map for the C73–C73′ disulfide bond in Trx-red
(contoured at 1.0σ above the mean value for the map). (b)
Difference electron density map between Trx-red and C73S for
residue 73. Only positive electron density is shown (contoured
at 2.7σ). (Figure produced with FRODO [[4]71 and [5]72].)
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Figure 7.
Figure 7. Stereoviews of (a) reduced and (b) oxidized human
thioredoxin active sites. Atom types are distinguished by
circles of differing size (C=O
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The above figures are
reproduced from the cited reference
with permission from Cell Press
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