Miscellaneous999: 9月 2024

2024年9月13日星期五

Selenocysteine

Selenocysteine is a structure formed when the sulfur in cysteine is replaced by selenium. As a result of this substitution, selenocysteine has a lower reduction potential than cysteine and is more suitable as an antioxidant. Selenocysteine is a crucial amino acid in the composition of selenoproteins, which are found in both prokaryotes and eukaryotes. Consequently, selenocysteine is now considered one of the basic amino acids that make up proteins. In other words, proteins are no longer composed of just 20 amino acids, but 21!

A well-known selenoprotein is glutathione peroxidase, which is responsible for reducing hydrogen peroxide (H2O2) to water. Although selenocysteine is a basic amino acid in protein composition, unlike the other twenty amino acids, it doesn't have its own genetic codon. Instead, it uses UGA (a stop codon) along with a roughly sixty-base "selenocysteine insertion sequence" (SECIS element) as a signal for inserting selenocysteine. In prokaryotes, the SECIS element is located close to the UGA codon. In archaea and eukaryotes, the SECIS element is often found in the 3' untranslated region (3'-UTR) of the messenger RNA (mRNA).

Source: Wikipedia

When selenium is absent, the translation of selenoproteins stops at the UGA codon, resulting in incomplete, non-functional proteins. Only when selenium is present can complete proteins be produced. Selenocysteine was discovered in 1976 by Thressa Stadtman of the National Institutes of Health (NIH). She and her husband were the first married couple at NIH, each with their own laboratory, and the two labs also collaborated.

For the origin of cysteine, please refer to "Cysteine and Bladder." The "seleno-" in selenocysteine obviously comes from selenium, though "seleno-" is not a prefix. However, due to its association with selenoproteins, it seems to have been widely adopted.

References:

Wikipedia. Selenocysteine, Thressa Stadtman, SECIS element.

pyrrolysine: the 22nd standard amino acid???

Source: Wikipedia

The world is constantly changing, altering our understanding from past textbooks. The nine planets became eight, twelve pairs of cranial nerves are now thirteen, and the discovery of selenocysteine increased the standard protein amino acids from twenty to twenty-one. However, the discovery of pyrrolysine in archaea and some bacteria in 2002 once again challenged the composition of standard protein amino acids. Some scientists argue that pyrrolysine should be considered the twenty-second amino acid, while others disagree; after all, only methane-producing archaea and some bacteria (including E. coli) use pyrrolysine.

In 2002, scientists discovered pyrrolysine at the active site of methyltransferase in Methanosarcina barkeri. Later, pyrrolysine was found in many methyltransferases; its function in enzymes may be to help adjust the position of methyl groups for reaction with cofactors. Unlike hydroxyproline, pyrrolysine has a genetic code, UAG. Readers might exclaim: Wait! Isn't UAG one of the stop codons? Yes, it is. However, like selenocysteine using UGA, pyrrolysine's use of UAG requires special equipment.

Microorganisms capable of using pyrrolysine carry a special transfer RNA (tRNA) that bears pyrrolysine and has an anticodon to recognize UAG. Moreover, this unique tRNA has its own dedicated aminoacyl-tRNA synthetase (aaRS) responsible for attaching pyrrolysine. Pyrrolysine is synthesized from two lysines and, due to its pyrrolidine structure (see proline), it has the prefix "pyrro-" in its name.

The microbial world is fascinating, and the microorganisms we can cultivate in laboratories likely represent only a small fraction of all microbes. Perhaps in the future, with a better understanding of microorganisms and deep-sea life, we might discover more unique amino acids, and the list of standard protein amino acids may grow even longer!

References:

Wikipedia. Pyrrolysine.

Srinivasan, G; James, C. M.; Krzycki, J. A. 2002. Pyrrolysine encoded by UAG in Archaea: charging of a UAG-decoding specialized tRNA. Science. 296 (5572): 1459–1462. doi:10.1126/science.1069588