Selenium and Selenocysteine in Protein Chemistry

Abstract

Selenocysteine, the selenium-containing analogue of cysteine, is the twenty-first proteinogenic amino acid. Since its discovery almost fifty years ago, it has been exploited in unnatural systems even more often than in natural systems. Selenocysteine chemistry has attracted the attention of many chemists in the field of chemical biology owing to its high reactivity and resulting potential for various applications such as chemical modification, chemical protein (semi)synthesis, and protein folding, to name a few. In this Minireview, we will focus on the chemistry of selenium and selenocysteine and their utility in protein chemistry.

Substitution of an Internal Disulfide Bridge with a Diselenide Enhances both Foldability and Stability of Human Insulin

“…The selenol group of Sec has a lower p K a (near 5.2) and a lower reduction potential ( E 0 =−386 mV) than does the thiol group of Cys. Pairwise Cys‐to‐Sec substitutions have been found in several cases to enhance the oxidative folding of proteins– as well as the efficient use of Se‐containing reagents . Furthermore, because diselenide bonds are more stable than disulfides (relative to their respective reduced forms), substituting Sec residues in strategic positions can improve folding efficiency even via non‐native pairing followed by protein structure‐driven rearrangement .…”

Miklós Bodanszky Award Lecture: Selective chalcogen chemistry to study protein science

“…Below, we describe three recent cases from our lab's work where chalcogens were harnessed to give valuable insight into the protein that contained them. For further studies on the subject, the readers are advised to read excellent reviews from several research groups including the groups of Holmgren, Moroder, Alewood, Payne, Rozovsky, Reich and Hondal, Hilvert, and our own …”

“…For further studies on the subject, the readers are advised to read excellent reviews from several research groups including the groups of Holmgren, 1 Moroder, 2 Alewood, 3 Payne, 4 Rozovsky, 5 Reich and Hondal, 6 Hilvert, 7,8 and our own. 9 In "The Case of BPTI," we describe how locking a disulfide bond with a stable methylene thioacetal bridge both stabilized a folded protein without affecting its function or structure and uncovered a hidden pathway in the folding mechanism of the well-studied bovine pancreatic trypsin inhibitor (BPTI). For "The Case of Selenoinsulin," we show how carefully designing a disulfide-to-diselenide bond substitution can enhance both protein folding and protein stability while maintaining its structure and function.…”

A Facile Method for Producing Selenocysteine‐Containing Proteins

“…Selenocysteine (Sec, U) is a fascinating building block for recombinant proteins: [1] it is more active and more resistant to irreversible overoxidation than cysteine (Cys), [2] is chemically modifiable, [3] and a diselenide bond is more stable than a disulfide bond in proteins. [4] Sec residues in proteins can be chemically converted into different amino acid side chains via a dehydroalanine intermediate.…”