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PDBsum entry 1dnc
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Oxidoreductase
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PDB id
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1dnc
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References listed in PDB file
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Key reference
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Title
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Enzyme inactivation through sulfhydryl oxidation by physiologic no-Carriers.
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Authors
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K.Becker,
S.N.Savvides,
M.Keese,
R.H.Schirmer,
P.A.Karplus.
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Ref.
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Nat Struct Biol, 1998,
5,
267-271.
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PubMed id
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Abstract
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Nitric oxide (NO) is a pluripotent regulatory molecule, yet the molecular
mechanisms by which it exerts its effects are largely unknown. Few physiologic
target molecules of NO have been identified, and even for these, the
modifications caused by NO remain uncharacterized. Human glutathione reductase
(hGR), a central enzyme of cellular antioxidant defense, is inhibited by
S-nitrosoglutathione (GSNO) and by diglutathionyl-dinitroso-iron (DNIC-[GSH]2),
two in vivo transport forms of NO. Here, crystal structures of hGR inactivated
by GSNO and DNIC-[GSH]2 at 1.7 A resolution provide the first picture of enzyme
inactivation by NO-carriers: in GSNO-modified hGR, the active site residue Cys
63 is oxidized to an unusually stable cysteine sulfenic acid (R-SOH), whereas
modification with DNIC-[GSH]2 oxidizes Cys 63 to a cysteine sulfinic acid
(R-SO2H). Our results illustrate that various forms of NO can mediate distinct
chemistry, and that sulfhydryl oxidation must be considered as a major mechanism
of NO action.
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