Chemical Basis for the Use of Selenocysteine

Ruggles, Erik L.; Snider, Gregg W.; Hondal, Robert J.

doi:10.1007/978-1-4614-1025-6_6

Cited by 15 publications

(29 citation statements)

References 20 publications

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“…Overall, in the presence of EDTA, GPx1’s Sec is stable and not prone to hyperoxidation or selenium elimination. This is in agreement with several reports about selenoproteins resistance to inactivation by oxidants [12, 34, 35]. …”

Section: Resultssupporting

confidence: 94%

RETRACTED: Glutathione peroxidase׳s reaction intermediate selenenic acid is stabilized by the protein microenvironment

Rozovsky

2014

Free Radical Biology and Medicine

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Selenenic acids are highly reactive intermediates of selenoproteins’ enzymatic reactions. Knowledge of how the protein environment protects and stabilizes them is fundamental not only to descriptions of selenoproteins’ reactivity but also potentially for proteomics and therapeutics. However, selenenic acids are considered particularly short-lived and were not yet identified in wild-type selenoproteins. Here, we report trapping the selenenic acid in glutathione peroxidase, an anti-oxidant enzyme that efficiently eliminates hydroperoxides. It has long been thought that selenium-containing glutathione peroxidases form a selenenic acid intermediate. However, this putative species has eluded detection. Here, we report its identification. The selenenic acid in bovine glutathione peroxidase 1 was chemically trapped using dimedone, an alkylating agent specific to sulfenic and selenenic acids. The alkylation of the catalytic selenocysteine was verified by electrospray ionization mass spectrometry. In the presence of glutathione, the selenocysteine was not alkylated because the selenenic acid condenses faster with glutathione than the alkylation reaction. In the absence of thiols, the selenenic acid was surprisingly long-lived with 95% of the protein still able to react with dimedone 10 min after hydrogen peroxide was removed, indicating that the protein environment stabilizes the selenenic acid by shielding it from reactive groups in the protein. After 30 min, the selenocysteine was no longer modified but became accessible once the protein was exposed to reducing agents. This suggests that the selenenic acid reacted with a protein’s amide or amine to form a selenylamide bond. Such a modification may play a role in protecting glutathione peroxidase’s reactivity.

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Section: Resultssupporting

confidence: 94%

RETRACTED: Glutathione peroxidase׳s reaction intermediate selenenic acid is stabilized by the protein microenvironment

Rozovsky

2014

Free Radical Biology and Medicine

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“…Selenocysteine is mostly used in enzymes that catalyze redox reactions. Compared to cysteine, selenocysteine is less susceptible to complete oxidation, which lowers the risk of enzyme deactivation (Ruggles et al 2012). Important examples of such enzymes include hydrogenases and glutathione peroxidase.…”

Section: Selenium In Biologymentioning

confidence: 99%

Selenium Isotopes as a Biogeochemical Proxy in Deep Time

Stüeken

2017

Reviews in Mineralogy and Geochemistry

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“…This suggests that selenium has different chemical reactivity compared to sulfur, which enables it to mimic a peroxidase. It was suggested that these chemical properties are higher nucleophilicity and higher electrophilicity relative to sulfur (69). A good example of this is the peroxidase activity of selenomethionine (3,43,81).…”

Section: Why Selenium Is Used In Peroxidase Enzymesmentioning

confidence: 99%

“…This is highly desirable, for if this was not the case the sulfenic acid intermediate could be further oxidized to a sulfinic acid residue (Cys-SO 2 -). The oxidation of a Cys residue to a Cys-SO 2 -residue is irreversible because it cannot be reduced back to the reduced Cys-SH state, but it can be further oxidized to a Cys-sulfonic acid residue Cys-SO 3 - (69). Oxidation either to Cys-SO 2 -or Cys-SO 3 -would result in an enzyme that is permanently inactivated (69).…”

Section: Fig 7 Description Of the ''Seleno Effect'' (A)mentioning

confidence: 99%

Selenocysteine in Thiol/Disulfide-Like Exchange Reactions

Hondal

Marino

Gladyshev

2013

Antioxidants & Redox Signaling

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153

119

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Significance: Among trace elements used as cofactors in enzymes, selenium is unique in that it is incorporated into proteins co-translationally in the form of an amino acid, selenocysteine (Sec). Sec differs from cysteine (Cys) by only one atom (selenium versus sulfur), yet this switch dramatically influences important aspects of enzyme reactivity. Recent Advances: The main focus of this review is an updated and critical discussion on how Sec might be used to accelerate thiol/disulfide-like exchange reactions in natural selenoenzymes, compared with their Cys-containing homologs. Critical Issues: We discuss in detail three major aspects associated with thiol/ disulfide exchange reactions: (i) nucleophilicity of the attacking thiolate (or selenolate); (ii) electrophilicity of the center sulfur (or selenium) atom; and (iii) stability of the leaving group (sulfur or selenium). In all these cases, we analyze the benefits that selenium might provide in these types of reactions. Future Directions: It is the biological thiol oxidoreductase-like function that benefits from the use of Sec, since Sec functions to chemically accelerate the rate of these reactions. We review various hypotheses that could help explain why Sec is used in enzymes, particularly with regard to competitive chemical advantages provided by the presence of the selenium atom in enzymes. Ultimately, these chemical advantages must be connected to biological functions of Sec.

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Chemical Basis for the Use of Selenocysteine

Cited by 15 publications

References 20 publications

RETRACTED: Glutathione peroxidase׳s reaction intermediate selenenic acid is stabilized by the protein microenvironment

RETRACTED: Glutathione peroxidase׳s reaction intermediate selenenic acid is stabilized by the protein microenvironment

Selenium Isotopes as a Biogeochemical Proxy in Deep Time

Selenocysteine in Thiol/Disulfide-Like Exchange Reactions

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