Oxidation of zinc-binding cysteine residues in transcription factor proteins.
Recent results on the oxidation of cysteine residues that bind zinc in transcription factors and their analogous peptides and in related proteins and model systems are reviewed. Two classes of oxidants, the transition metals and dioxygen, hydrogen peroxide, and related species, are considered, and the role of metal ions in suppressing or enhancing Cys oxidation is a major focus. Cysteines in the zinc-bound structures of transcription factors are less susceptible to oxidation than in the metal-free form, and this appears to correlate with reduced accessibility of the thiolates to oxidants. Substitution of other metal ions for Zn(II) increases the rate of Cys oxidation, apparently through increased oxidant accessibility. Reactions that result in reversible or irreversible oxidation of these zinc-binding cysteines under biological conditions are identified in the context of deleterious implications for gene expression.
Wilcox
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DE
Department of Chemistry, Dartmouth College, Hanover, NH 03755, USA. dean.e.wilcox@dartmouth.edu
Schenk
A D
AD
Feldman
B M
BM
Xu
Y
Y
D000595:Amino Acid Sequence; D000975:Antioxidants / Q000494:pharmacology; D001665:Binding Sites; D003035:Cobalt / Q000737:chemistry; D003545:Cysteine / Q000737:chemistry*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007501:Iron / Q000737:chemistry; D008667:Metalloproteins / Q000378:metabolism; D008668:Metallothionein / Q000737:chemistry / Q000502:physiology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009532:Nickel / Q000737:chemistry; D016877:Oxidants / Q000494:pharmacology; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism / Q000494:pharmacology; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D013439:Sulfhydryl Reagents / Q000378:metabolism / Q000494:pharmacology; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism; D015032:Zinc / Q000737:chemistry; D016335:Zinc Fingers / Q000502:physiology*
D000975:Antioxidants; D008667:Metalloproteins; D016877:Oxidants; D013439:Sulfhydryl Reagents; D014157:Transcription Factors; D003035:Cobalt; D009532:Nickel; D008668:Metallothionein; D006861:Hydrogen Peroxide; D007501:Iron; D015032:Zinc; D003545:Cysteine; D010100:Oxygen