aminoacyl-tRNA synthetases
Our genome codes for 20 different amino acids (using a three-base system called a codon), but the encoding
system ends up with 61 different codes for these 20 amino acids, so the molecules that must recognize these
codons needs to be able to place the correct amino acid with the correct tRNA molecule efficiently and with
a low error rate.
If our cells could use a lookup table this process would be much simpler, but instead it must use
electromagnetic interactions and shape as its primary methods of marrying the correct molecules.
The molecules that connect the amino acid to the corresponding tRNA are called aminoacyl-tRNA
synthetases, and the process is called aminoacylation (because of the carboxyl group on the amino acid
(“acyl”) that is covalently attached to the 3' end of the tRNA molecule).1
In addition to using the anticodon to match these molecules, the enzymes have other methods of pairing,
including using other bases. Base 73, for example, has been called the “discriminator base” because of its use
in determining a match (discrimination). Methylation of bases is another method used to help distinguish
molecules so that a correct match between similar tRNAs.
Both positive and negative electromagnetic interactions help detection of the correct tRNAs to their
corresponding enzyme. Shape also plays a role here. Many biological processes use shape to detect a
molecular match. We see this is in taste and smell, hormone detection, molecular channels, and other areas.
A molecule that is too large to fit into a pocket is easy to rule out, but one that is smaller must be
discriminated in other ways. A mechanism employed by these synthetases is to have a secondary pocket
that allows these erroneous molecules to swing into so they can be cleaved, allowing the correct molecule to
then bond.2
To further complicate matters, it was recently discovered that not all organisms code for all twenty
necessary synthetases and sometimes use alternate methods to “charge” the amino acids to the tRNAs. In
one known case in some bacteria, glutamine is created in “post-production” by an enzyme that converts
glutamic acid which was charged onto both the glutamine tRNAs and the glutamic acid tRNAs. Apparently,
this enzyme, called glutamyl-tRNA synthetase, can recognize the tRNAs with the incorrect amino acid and
convert it post hoc.3
1 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373986/
2 PDB-101: Molecule of the Month: Aminoacyl-tRNA Synthetases (rcsb.org)
3 https://www.pnas.org/doi/10.1073/pnas.0611611104