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PDBsum entry 2e2m
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Oxidoreductase
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PDB id
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2e2m
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References listed in PDB file
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Key reference
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Title
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Oxidation of archaeal peroxiredoxin involves a hypervalent sulfur intermediate.
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Authors
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T.Nakamura,
T.Yamamoto,
M.Abe,
H.Matsumura,
Y.Hagihara,
T.Goto,
T.Yamaguchi,
T.Inoue.
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Ref.
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Proc Natl Acad Sci U S A, 2008,
105,
6238-6242.
[DOI no: ]
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PubMed id
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Abstract
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The oxidation of thiol groups in proteins is a common event in biochemical
processes involving disulfide bond formation and in response to an increased
level of reactive oxygen species. It has been widely accepted that the oxidation
of a cysteine side chain is initiated by the formation of cysteine sulfenic acid
(Cys-SOH). Here, we demonstrate a mechanism of thiol oxidation through a
hypervalent sulfur intermediate by presenting crystallographic evidence from an
archaeal peroxiredoxin (Prx), the thioredoxin peroxidase from Aeropyrum pernix
K1 (ApTPx). The reaction of Prx, which is the reduction of a peroxide, depends
on the redox active cysteine side chains. Oxidation by hydrogen peroxide
converted the active site peroxidatic Cys-50 of ApTPx to a cysteine sulfenic
acid derivative, followed by further oxidation to cysteine sulfinic and sulfonic
acids. The crystal structure of the cysteine sulfenic acid derivative was
refined to 1.77 A resolution with R(cryst) and R(free) values of 18.8% and
22.0%, respectively. The refined structure, together with quantum chemical
calculations, revealed that the sulfenic acid derivative is a type of sulfurane,
a hypervalent sulfur compound, and that the S(gamma) atom is covalently linked
to the N(delta1) atom of the neighboring His-42. The reaction mechanism is
revealed by the hydrogen bond network around the peroxidatic cysteine and the
motion of the flexible loop covering the active site and by quantum chemical
calculations. This study provides evidence that a hypervalent sulfur compound
occupies an important position in biochemical processes.
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Figure 3.
Interaction of the hypervalent intermediate with surrounding
residues.
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Figure 4.
Structural change and putative reaction scheme of ApTPx.
(a–c) Close-ups around the peroxidatic cysteine residues of
the reduced, preoxidation, and hypervalent sulfur forms,
respectively. (d) Superimposition of the reduced (green) and
hypervalent sulfur (purple) forms. Proposed reaction scheme of
ApTPx is shown in e. Cso represents the C[p] residue in the
hypervalent sulfur form.
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