Threonyl-tRNA Synthetase Structure

            The folding topology of the entire protein in its most basic form appears to be L shaped.  According to SCOP the folding of Threonyl-tRNA synthetase is an alpha and beta protein (a+b).  This folding topology includes beta sheets that are mostly anti-parallel.  The alpha helices and beta sheets are mostly segregated.

            The active site of Threonyl-tRNA synthetase is classified by SCOP as a Class II aminoacyl-tRNA synthetase catalytic domain.  All class II amino-acyl-tRNA synthetase enzymes share these similar characteristics:

1. acylate at the 3’-hydroxyl group of the terminal adenosine of tRNA.

2. bind ATP with a similar conformation

3. tends to be dimeric

Threonyl-tRNA synthetase is highly selective to bind to the amino acid threonine.  It accomplishes this high selectivity with in the topology of its active site.  Threonyl-tRNA synthetase has zinc ion that is bound through a coordinate bond with two histines (His511 and His385) residues and one cysteine (Cys334) residue (Sankaranarayanan et al., 2000).  The zinc ion then provides a way for threonine to coordinately bond to Zn with its main chain amino group (Sankaranarayanan et al., 1999).  The side-chain hydroxyl from the threonine can then hydrogen bond to the Arginine – 520 residue.  This interaction at the active site causes threonyl-tRNA synthetase to be very selective to threonine.  The active site is surrounded on one side by anti-parallel beta-sheets and alpha helices on the opposite side (Berg, 2002).

Threonyl-tRNA Synthetase Function

Threonyl-tRNA synthetase is involved in protein synthesis, more specifically translation of the nucleotide sequence to the amino acid sequence.  This cellular process of translation occurs in the rough ER near the ribosomes.  Threonyl-tRNA synthetase is catalytically involved in the reaction that combines the amino acid with tRNA to form threonyl-tRNA.  Threonyl-tRNA synthetase does this by binding ATP and threonine to form a Threonine-AMP structure within the active site.  This threonyl-AMP then reacts with the threonyl-tRNA to from threonyl-tRNA plus the AMP.  This mechanism with an acyl adenylate intermediate is used for all other aminoacyl-tRNA synthases as well as fatty acid activation.  The specifics of how the active sites binds threonine is stated above.

            In consideration of thermodynamics this reaction would not occur spontaneously without the hydrolysis of ATP to AMP and pyrophosphate.  This reactions Gibbs free energy value at standard state is very close to zero.  When this reaction is coupled with the hydrolysis of pyrophosphate the reaction becomes very exergonic.