Glutaminyl-tRNA Synthetase
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Aminoacyl-tRNA synthetases in general are found in the cytoplasm and mitochondria. These biosynthetic enzymes attach a specific amino acid to the correlating tRNA molecule. These aminoacyl-tRNAs then move to ribosomes where they are ordered according to the mRNA sequence and transfer their amino acids for use in mRNA translation. Aminoacyl-tRNAs will bind to a codon on mRNA through its anticodon (on the tRNA) to facilitate the assembly of a protein molecule. The function of these enzymes is imperative for specific synthesis of proteins. An aminoacyl-tRNA synthetase binds ATP, tRNA, and an amino acid.

Glutaminyl-tRNA synthetase specifically recognizes glutamine and facilitates its binding to tRNA.

View Glutaminyl-tRNA Synthetase bound to tRNA ligand and ATP (Backbone View: Blue=protein, Green=tRNA)

View Glutaminyl-tRNA Synthetase bound to tRNA ligand and ATP (2 Dimentional Structure)
Note that the protein is predominantly alpha-helices on one side and beta-sheets on the other. The beta-sheet area helps facilitate the binding of glutamine.

Activate ATP
Deactivate ATP

The enzyme weighs 63.4 kD and it consists of 553 residues. It is class I monomeric enzyme. Class I aminoacyl-tRNA synthetases in general are usually monomeric and attach the amino acid to the 2’-OH of the terminal adenylate residue of the tRNA, then shifting it to the 3’-OH. They also have active site structures based on a Rossman fold (a parallel beta-sheet nucletide-binding fold).

In order to operate correctly, Glutaminyl-tRNA synthetase must successfully recognize glutamine and its correct cognate tRNA with a very high degree of specificity. V.L. Rath, et. al published an article in Structure discussing the mechanism that allows glutaminyl-tRNA synthetase to select glutamine over all other amino acids, including glutamic acid and glutamate. The hydroxyl group of Tyr211 and a water molecule facilitate the recognition of the two hydrogen atoms of nitrogen on the glutamine side chain.

Highlight Tyr 211 (red)

Prior to this recognition, the terminal nucleotide of the tRNA, A76, must pack against Tyr211 to achieve proper orientation and form part of the amino acid binding site.

Highlight A76 (red)

A sequence of three specific recognition elements allows the enzyme to recognize the correct tRNA molecule. These elements include contact with the discriminator base (unpaired base preceding CCA end), acceptor stem, and anticodon. Anticodon recognition focuses on the center U of the CUG anticodon.

Another interesting piece of information gathered using quanta/CHARrm is the comparison of the minimization energies of the active and inactive form of the protein when not bound to the tRNA strand. When the tRNA strand is removed, the active conformation of the protein has a Charmm energy of +58877.7617.

View the "active" protein (not bound to tRNA)
Click here to view a Ramachandran plot of this molecule.

If the unbound protein is minimized using the CHARrm minimization program, the CHARrm energy is found to be -18457.2057. The protein is "closes" the active site, making the protein inactive.

View the "inactive" protein (not bound to tRNA)
Click here to view a Ramachandran plot of this molecule.

The bound protein CHARrm energy was not calculated due to restraints in the program; however, a Ramachandran plot was calculated. Lipophillic and Electrostatic models were also created, but the rendering did not show anything interesting (even though the binding to the tRNA strand happens because of electrostatic interactions and the hydrophobic effect). (If you would like to see these models, you can access them by clicking on the right mouse button while the cursor is over the molecule image. Select 'select', 'display list', then 'create molecular surface.')