By the mid-1980s, there was general agreement that the protein synthetic machinery uses just 20 amino acid building blocks to make proteins. Many modified amino acids were known to be present in proteins but these were formed by modifying amino acid residues after the polypeptide chain was formed. Therefore, it was a great surprise when selenocysteine (Sec) was identified as the 21st amino acid. This rare amino acid, an analog of cysteine in which the element selenium replaces sulfur, is present in a few proteins, mostly oxidoreductases, from eukaryotes, bacteria, and archaeons.
The bacterial pathway for selenocysteyl-tRNASec formation, which was elucidated largely through the efforts of August Böck and coworkers beginning in 1986. The three steps in this pathway are as follows: (1) Selenophosphate synthetase catalyzes the synthesis of selenophosphate from ATP and selenide, (2) Ser-tRNA synthetase attaches a séryl group to tRNASec, and (3) Selenocysteine synthase catalyzes a pyridoxal phosphate- dependent conversion of selenophosphate and Ser-tRNASec to selenocystcyl- tRNASec. The tRNASec species contains up to 100 nucleotides, making it the longest known tRNA. It also has other unusual features. For example, it has one more nucleotide base pair in its acceptor arm than most other tRNAs and an extended D-arm. Because of these unique features, selenocysteyl- tRNASec is not recognized by elongation factor 1A (EF1A) (see Chapter 20), and requires its own special elongation factor.
A second unusual amino acid building block, pyrrolysine, was independently discovered by Joseph A. Krzycki and coworkers and Michael K. Chan and coworkers in 2002. Although details of the pathway for pyrrolysine -tRNA formation must still be worked out preliminary data suggest that lysine is first attached to a special tRNA and then modified. Thus far, pyrrolysine has only been observed in archaeons that generate methane.