Aminoacyl tRNA synthetase for aspartic acid (Class II aaRS). It is a dimer of two identical subunits (blue and green); tRNA molecules are shown in red. (more details...)

An aminoacyl tRNA synthetase (aaRS) is an enzyme that catalyzes the esterification of a specific amino acid or its precursor to one of all its compatible cognate tRNAs to form an aminoacyl-tRNA.

Mechanism

The synthetase first binds ATP and the corresponding amino acid or its precursor to form an aminoacyl-adenylate and release inorganic pyrophosphate (PP_i). The adenylate-aaRS complex then binds the appropriate tRNA molecule, and the amino acid is transferred from the aa-AMP to either the 2'- or 3'-OH of the last tRNA base (A76) at the 3'-end. Some synthetases also mediate a proofreading reaction to ensure high fidelity of tRNA charging; if the tRNA is found to be improperly charged, the aminoacyl-tRNA bond is hydrolyzed.

Reaction

Reaction:

1. amino acid + ATP ? aminoacyl-AMP + PPi
2. aminoacyl-AMP + tRNA ? aminoacyl-tRNA + AMP

Sum of 1 and 2: amino acid + tRNA + ATP ? aminoacyl-tRNA + AMP + PPi

Classes

There are two classes of aminoacyl tRNA synthetase:^[1]

• Class I has two highly conserved sequence motifs. It aminoacylates at the 2'-OH of an adenosine nucleotide, and is usually monomeric or dimeric (one or two subunits, respectively).
• Class II has three highly conserved sequence motifs. It aminoacylates at the 3'-OH of the same adenosine, and is usually dimeric or tetrameric (two or four subunits, respectively). Although phenylalanine-tRNA synthetase is class II, it aminoacylates at the 2'-OH.

The amino acids are attached to the hydroxyl (-OH) group of the adenosine via their carboxyl (-COOH) groups.

Regardless of where the aminoacyl is initially attached to the nucleotide, the 2'-O-aminoacyl-tRNA will ultimately migrate to the 3' position via transesterification.

Structures

Both classes of aminoacyl-tRNA synthetases are multidomain proteins. Typically, an aaRS consists of a catalytic domain (where both the above reactions take place) and an anticodon binding domain (which mostly interacts with the anticodon region of the tRNA and ensures binding of the correct tRNA to the protein). In addition, some aaRSs have additional RNA binding domains and editing domains^[2] that cleave incorrectly paired aminoacyl-tRNA molecules.

The catalytic domains of all the aaRSs of a given class are found to be homologous to one another, while class I and class II aaRSs are unrelated to one another. The class I aaRSs have the ubiquitous Rossmann fold and have the antiparallel beta-strands architecture while the class II aaRSs have a unique fold made up of antiparallel beta-strands.

Evolution

Most of the aaRSs of a given specificity are evolutionarily closer to one another than to aaRSs of another specificity. However, AsnRS and GlnRS group within AspRS and GluRS respectively. Most of the aaRSs of a given specificity also belong to a single class. However, there are two distinct versions of the LysRS - one belonging to the class I family and the other belonging to the class II family.

In addition, most of the aaRSs of a given specificity display the so-called canonical phylogenetic pattern in which the enzymes are grouped by the three domains of life - Archaea, Bacteria, and Eukarya, and the root of the phylogenetic tree is present in between the Bacterial branch and the Archaeal/Eukaryal branch.

References

1. ^ "tRNA Synthetases". Retrieved on 2007-08-18.
2. ^ "High Fidelity". Retrieved on 2007-08-18.

External links

• MeSH Amino+Acyl-tRNA+Synthetases

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