William Franks, Payal Patel, Elizabeth Daubert
The general reaction which binds an amino acid of its precursor to the correct tRNA
involves the enzyme aminoacyl tRNA synthetase. The enzyme first adenylates the amino acid to
form aminoacyl adenylate, and then adds the aminoacyl adenylate to the correct tRNA. Another
method is charging a tRNA with a precursor by a nondiscriminatory aarS, then nonsynthetase
enzymes convert the aa while it is bound with the tRNA.
There are twenty aaRS’s, divided into two classes of 10. Each one is specific, and classes
have class-speicifc active sites and different structures which ensure that classes do not bind aa’s
and tRNAs from other classes. Class II has an active site with an antiparallel B sheet with
helices. The aaRS interacts with the acceptor stem of tRNA with insertion regions branching out
of the active site. Class II enzymes have three specific sequence motifs, and they bind to the 2’
OH of the adenosine of tRNA (except for PheRS). AaRS’s usually have a catalytic core domain
and a specific domain for tRNA binding.
AsRS recognizes tRNA by a GU wobble base pair in the acceptor stem. It also has an
editing mechanism in which larger amino acids are activated so slowly due to their fit with the
protein that they require no editing, but smaller aa’s such as Ser and Gly are often charged. The
editing domain hydrolyzes mischarged tRNAs and non-cognate AMP’s which keep it from
forming ser-tRNA and gly-tRNA. The tRNA recognition occurs in the Recognition module,
which is one of four domains: the three others are the c terminal oligomerization site, the editing
bay, and the active site.
Serine is an amino acid that is classified as polar. It is extremely important in the process
of metabolism. Seryl-tRNA synthetase is the enzyme which helps serine successfully bind to the
appropriate tRNA. There are at least five distinct codons on serine: UCU, UCC, UCA, UCG,
AGU, and AGC. Distinction between serine and other amino acids is insured by two structural
characteristics of the seryl-tRNA synthetase. The first is two distinct hydrogen-bond interactions
with the amino acid side chain hydroxyl group and the other is the small size of the binding
pocket, thus the pocket cannot accommodate anything more than the hydroxyl group. There is a
secondary specificity of serine as well. Discrimination during the aminoacylation transition state
of the complex, in addition to the fact that complexes do not exist long, means that there is a
rapid turnover and thus a greater specificity action.
Glycine is one of the basic amino acids. It is the smallest and is unique within the amino
acids because it is nonchiral. It is coed by codons: GGU, GGC, GGA and GGG. Most proteins
only use a very small amount of glycine. Glycine serves as an important neurotransmitter.
Glycyl-tRNA synthetase is the enzyme that binds Glycine to the correct tRNA. Glycyl-tRNA
synthetase has two distinct species, Alpha 2 dimer which is in humans and alpha 2 beta 2 dimer.
Glycine recognition by tRNA has to do with the fact that glycine lacking a substrate chain which
makes glycyl-tRNA exclude any side-chained amino acid from bonding to it, like alanine. Also it
has a negative pit that attracts the ammonia in glycine, therefore, glycine bonds to it. These two
ways are the recognition methods for glycyl-tRNA to bond with the correct amino acid. As
glycyl-tRNA synthetase focuses on recognition, glycine and glycyl-tRNA form strong hydrogen
bonds and strong electrostatic interactions with one another. If glycyl-tRNA recognizes the
wrong amino acid, then sometimes disastrous effects are produced, such as CMT which ends in
the atrophy of tissue in the body.