Selenium in proteins

The critical discovery that acetyl phosphate is generated and the information gained from several studies of each of the components of GR allowed an enzyme mechanism to be proposed (Arkowitz and Abeles 1991). However, with the current knowledge that one of the subunits of protein B also contains selenium, further work is needed to characterize the intermediates of the reaction and to explain the role of an additional selenocysteine residue. Whether this additional selenocysteine residue in protein B might serve as a direct reductant of the postulated thioselenide derivative of selenoprotein A and possibly serve as a link to the Trx-TrxR system is unknown. It should also be noted that the selenium-limited cultures that were initially studied during analysis of selenoprotein A (Turner and Stadtman 1973) apparently contained active fractions of proteins B and C, suggesting the role for selenium in protein B may not prove to be absolutely necessary for enzyme catalysis. 

C. C. Chery, H. Chassaigne, L. Verbeeck, R. Cornelis, F. Vanhaecke, L. Moens, Detection and quantiPcation of selenium in proteins by means of gel electrophoresis and electrothermal vaporization ICP-MS, J. Anal. Atom. Spectrom., 17 (2002), 576D580. 

Vezina D, Belanger R, Bleau G. 1990. Microdetermination of selenium in protein fractions isolated by analytical methods. Biol Trace Elem Res 24(2) 153-162. 

Enzymes often need for their activity the presence of a non-protein portion, which may be closely combined with the protein, in which case it is called a prosthetic group, or more loosely associated, in which case it is a coenzyme. Certain metals may be combined with the enzyme such as copper in ascorbic oxidase and selenium in glutathione peroxidase. Often the presence of other metals in solution, such as magnesium, are necessary for the action of particular enzymes. 

Replacement of Sulfur by Selenium in Iron Sulfur Proteins Jacques Meyer, Jean-Marc Moulis, Jacques Gaillard, and Marc Lutz... 

All selenium-containing proteins and enzymes in animals, microorganisms and plants incorporate selenocysteine non-specifically105 or as part of Se-dependent antioxidant enzymes such as glutathione peroxidase, (EC 1.11.1.9) which has a Se-cysteine residue in its active site.116 120 An active form of Se, selenophosphate, is produced by selenophosphate synthetase in several bacteria. This active form is required for the production of Secys-tRNA, a precursor for Se-cysteine.121 In a similar vein, a Se-containing modified-tRNA nucleoside, 5-methylaminomethyl-2-selenouridine, encodes a selenouridine synthase which replaces sulfur in tRNA with selenium.122... 

Wrench, J.J. and N.C. Campbell. 1981. Protein bound selenium in some marine organisms. Chemosphere 10 1155-1161. 

The vast majority of research focused on selenium in biology (primarily in the fields of molecular biology, cell biology, and biochemistry) over the past 20 years has centered on identification and characterization of specific selenoproteins, or proteins that contain selenium in the form of selenocysteine. In addition, studies to determine the unique machinery necessary for incorporation of a nonstandard amino acid (L-selenocysteine) during translation also have been central to our understanding of how cells can utilize this metalloid. This process has been studied in bacterial models (primarily Escherichia colt) and more recently in mammals in vitro cell culture and animal models). In this work, we will review the biosynthesis of selenoproteins in bacterial systems, and only briefly review what is currently known about parallel pathways in mammals, since a comprehensive review in this area has been recently published. Moreover, we summarize the global picture of the nonspecific and specific use of selenium from a broader perspective, one that includes lesser known pathways for selenium utilization into modified nucleosides in tRNA and a labile selenium cofactor. We also review recent research on newly identified mammalian selenoproteins and discuss their role in mammalian cell biology. 

We now have clear evidence that selenium can be introduced specifically into proteins as selenocysteine and into a subset of tRNA species as mnm Se U or Se2U. The pathways and molecular mechanisms for insertion of selenium into these molecules have been well established in several model systems, the best studied being E. coli. The role for selenium in selenoproteins (i.e., the need for selenium over sulfur) is thought to be its ability to act as a more reactive nucleophile and perhaps a more rapid catalyst. However, a void in our knowledge exists for the specific need for selenium-modified tRNAs. Mutation of either selD or ybbB did not alter the growth characteristics of E. coli- however, no thorough analysis of the bacterial stress response has been carried out in any of these mutants. Clearly, further study is needed to better define the role for selenium in wobble codon usage for a subset of tRNA species. 

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