Selenocysteine in proteins -: properties and biotechnological use

Selenocysteine (See), the 21st amino acid, exists naturally in all kingdoms of life as the defining entity of selenoproteins. See is a cysteine (Cys) residue analogue with a selenium-containing selenol group in place. of the sulfur-containing thiol group in Cys. The selenium atom gives See quite different properties from Cys. The most obvious difference is the lower pK(a), of Sec, and See is also a stronger nucleophile than Cys. Proteins naturally containing See are often enzymes, employing the reactivity of the See residue during the catalytic cycle and therefore See is normally essential for their catalytic efficiencies. Other unique features of See, not shared by any of the other 20 common amino acids, derive from the atomic weight and chemical properties of selenium and the particular occurrence and properties of its stable and radioactive isotopes. See is, moreover, incorporated into proteins by an expansion of the genetic code as the translation of selenoproteins involves the decoding of a UGA codon, otherwise being a termination codon. In this review, we will describe the different unique properties of See and we will discuss the prerequisites for selenoprotein production as well as the possible use of See introduction into proteins for biotechnological applications. These include residue-specific radiolabeling with gamma or positron emitters, the use of See as a reactive handle for electophilic probes: introducing fluorescence or other peptide conjugates, as the basis for affinity purification of recombinant proteins, the trapping of folding intermediates, improved phasing in X-ray crystallography, introduction of Se-77 for NMR spectroscopy, or, finally, the analysis or tailoring of enzymatic reactions involving thiol or oxidoreductase (redox) selenolate chemistry. (c) 2005 Elsevier B.V All rights reserved.