Saturday, May 28, 2016

21st and 22nd Amino Acids?

Proteins are key players in many vital processes in living organisms. Functionally, they transport substances like hemoglobin, which carries oxygen to cells; some are enzymes, which catalyze metabolic reactions; hormones, which regulate body activities; pump ions or recognize signalling molecules; and some are antibodies, which protect our body. The complexity and variety of proteins is really unusually large, for example, there are more than 100,000 different proteins at work in our body. But almost all of them are made up of 20 different amino acids only.

www.vcmbc.com
The 20 amino acids that are encoded directly by the codons of the universal genetic code are called standard or canonical amino acids. The others are called non-standard or non-canonical. Most of the non-standard amino acids are also non-proteinogenic (i.e. they cannot be used to build proteins), but there are non-standard proteinogenic amino acids, as they can be used to build proteins by exploiting information not encoded in the universal genetic code.

The truth that there are amino acids, except for the 20 standard amino acids, that can be used for protein production in certain cases is really amazing. These non-standard proteinogenic amino acids: selenocysteine (21st) which is present in many non-eukaryotes as well as most eukaryotes, but not coded directly by DNA and pyrrolysine (22nd) which can be found only in some archaea and one bacterium). For example, 25 human proteins include selenocysteine (Sec) in their primary structure, and the structurally characterized enzymes (selenoenzymes) employ Sec as the catalytic moiety in their active sites. Pyl and Sec are encoded via variant codons. For example, Sec is encoded by stop codon and SECIS element.

Twenty-two amino acids are naturally incorporated into polypeptides and encoded by the universal genetic code while Sec and Pyl are incorporated into proteins by unique synthetic mechanisms. Sec is incorporated when the mRNA being translated includes a SECIS element, which causes the UGA codon to encode Sec instead of a stop codon.
bioinformatica.upf.edu

 It has been shown that in the case of selenocysteine, termination of translation is inhibited in the presence of a specific mRNA sequence in the 3'-region after the UGA-codon that forms a hairpin like structure (called "Sec insertion sequence" (SECIS)).

Pyl is used by some methanogenic archaea in enzymes that they use to produce methane. It is coded for with the codon UAG, which is normally a stop codon in other organisms. This UAG codon is followed by a PYLIS downstream sequence.

Sec and Pyl are rare amino acids that are co-translationally inserted into proteins and known as the 21st and 22nd amino acids in the genetic code. Sec and Pyl are encoded by UGA and UAG codons, respectively, which normally serve as stop signals.

Only a few highly specialized proteins additionally contain selenocysteine, the very rare 21st amino acid discovered in 1986. The researchers at the Technische Universitaet Muenchen have elucidated the structure of an important enzyme in the production of Pyl.

PYRROLYSINE
www.123rf.com
In 2002, the discovery of the 22nd amino acid in methane-producing archaea of the family Methanosarcinaceae was really a big surprise: Pyl. It is genetically encoded in a similar manner as that of Sec and the other 20. The archaea use the unusual amino acid in proteins that they need for energy conversion. Pyl is located in the catalytic center of the proteins and is essential for their function. The energy generation process of the archaebacteria would not work without Pyl.

The scientists at Ohio State University succeeded in deciphering parts of the manufacturing process of Pyl in March 2011. They proposed a reaction mechanism suggesting that the enzyme PylB catalyzes the first step of Pyl biosynthesis by converting the amino acid lysine to the intermediate product methylornithine. Scientists headed by Michael Groll, Professor of Biochemistry at the TUM-Department of Chemistry, could now determine the crystalline structure of PylB by X-ray using structure analysis.
PYRROLYSINE

www.chemspider.com


To their great surprise, they caught the enzyme in action: at the time of crystallization the reaction product, methylornithine, had not left the enzyme. It adhered to a confined space, a kind of "reaction vessel," still in connection with the centers of the enzyme responsible for its creation. "That the product was still present in the enzyme, was something special and a great stroke of luck," says Felix Quitterer, a member of the scientific staff at the Department of Biochemistry and lead author of the publication. "We were not only able to directly detect the methylornithine, but also retroactively reconstruct how it is created from the source amino acid lysine."

This reaction was not only unknown until now, it is also very difficult to catalyze. It is a cluster of four iron and four sulfur atoms in the active site that is the key to the conversion. "This is a really unusual enzymatic reaction. Up to now no chemist in the laboratory is able to synthesize methylornithine in a one-step reaction starting from lysine," says Groll.

The conversion of lysine to methylornithine is helping scientists to understand how archaebacteria can modify an existing system to enable the formation of a tailored amino acid that, when installed in the appropriate protein, catalyzes a very specific reaction.

As surfing over the net, this question really caught my attention, “Why does the vast complexity of proteins in living organisms come from only a few natural amino acids, even though the genetic code would be able to encode many more?” I’ve just thought to myself, He really put things in order. Some are capable for this, and some are for that.

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