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Synthetase

Synthetase

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About Synthetase:

Both synthase and synthetase were once used to describe enzymes that catalyze the synthesis of compounds in biological systems. The old view was that synthetases were enzymes that derived their energy for synthesis reactions (such as polymerization) from the ATP in nuclei of cells. In contrast, synthases did not use such an energy source.
Today, however, the definition has changed. Synthetases are distinct from synthases and are now used interchangeably with ligases. A common synthetase called aminoacyl-tRNA synthetase (and also tRNA-ligase) is an enzyme that attaches amino acids onto tRNA.

Synthetase Mechanism
During the first step of the process, the synthetase binds ATP and corresponding amino acid.
This process produces aminoacyl-adenylate and releases the inorganic compound pyrophosphate, sometimes abbreviated PP. The complex then binds to the appropriate tRNA molecule's D arm, where the amino acid is then converted from the aa-AMP to chemical groups at the ends of the tRNA nucleotide. The chemical structure on the tRNA determines the precise location of the activity.
The reaction that combines amino acids with tRNA and ATP and leads to AMP, PP, and aminoacyl-tRNA is highly exergonic. Sometimes, the result can lead to the wrong amino acid being added to the tRNA. In these cases, the bond is hydrolyzed, and then the cell has another chance to attempt to attach the correct protein precursor.

Synthetase Structure
Synthetases in the class we've discussed so far are classified as "multi-domain" proteins. Most have a catalytic domain where most of the reaction that we described above takes place, and a binding domain which interacts with sections of the tRNA.
Aminoacyl-tRNA synthetases can recognize the correct tRNAs that they need to target using both anticodons and also their overall structure and configuration. They also have additional RNA binding and editing domains that they can use to cleave incorrectly-paired aminoacyl-tRNA molecules.

Synthetase Functions
Synthetases have a variety of functions, especially in the biotech domain. For instance, researchers and companies can use synthetases to carry unnatural amino acids and synthesis them in the lab. They can also use synthetases to attach them to specific tRNAs, opening up the possibility of expanding the genetic code beyond the traditional twenty canonical amino acids. While research is still in its early stages, it opens up the opportunity to design new organisms in biologically and evolutionarily novel ways that have not yet been seen in the natural world.
Chemists have also found a variety of uses of synthetases. For instance, researchers investigating mutations of aminoacyl tRNA synthetases have expanded the genetic codes of a variety of organisms, allowing them to add all kinds of interesting properties, including photoreactive elements, fluorescence, redox-active amino acids, and xenon-chelating cells.
Understanding synthetase better may help to reverse some diseases. Already, scientists have associated synthetase with a range of genetic disorders such as Leigh syndrome, CAGSSS, and West syndrome.