Chemical Basis for the Use of Selenocysteine

Abstract

Since the discovery of selenocysteine as the 21st amino acid in the genetic code, two streams of thought have dominated the question of why selenium is used to replace sulfur in enzyme active sites in the form of selenocysteine. These ideas are that selenocysteine is (i) a “relic of the anaerobic world” and (ii) “catalytically superior” to the use of sulfur as cysteine. This latter idea is due to the experimental finding that the replacement of selenocysteine with cysteine in enzyme active sites results in a large drop in catalytic activity, and has been interpreted to mean that selenocysteine is essential for catalyzing the formation of product from substrate. We and others have previously proposed that selenocysteine is not catalytically essential since cysteine homologs of selenocysteine enzymes exist and catalyze their enzymatic reactions with comparable efficiency. Here, and elsewhere, we discuss the idea that the use of selenocysteine confers an enzyme with the ability to resist irreversible inactivation by oxidation.