Template-based structure prediction and molecular dynamics simulation study of two mammalian Aspartyl-tRNA synthetases

Aminoacyl-tRNA synthetases (aaRSs) catalyze the esterification of a specific amino acid. There are two classes of aminoacyl-tRNA synthetases. Class I usually exists as a monomeric or dimeric form and has two highly conserved sequence motifs. Functionally, it aminoacylates at the 2′-OH of an adenosine nucleotide. While, class II normally exists as a dimeric or tetrameric form and consists of three highly conserved sequence motifs. It aminoacylates at the 3′-OH of the same adenosine. Aspartyl-tRNA synthetase (AspRS) belongs to class II aaRSs, is not only important to sustain the mechanism of protein fidelity by specifically recognizing its cognate amino acid; but also equally significant in the aminoacylation of tRNA^Asp. Several crystal structures of AspRS have been reported yet but no structural information is available for mammalian AspRS. In this study, we have applied template-based modeling/structure prediction to elucidate structural details of two mammalian AspRS from Homo sapiens and Mus musculus. The resultant models showed excellent stereochemistry similar to the crystal structure of yeast. A 5 ns molecular dynamics (MD) simulation was also performed to study the conformational changes occur in the flipping loop region (279-285). The root mean square fluctuation (RMSF) graph shows movements mostly in the catalytic site and in the flipping loop region while the main secondary structure maintained fairly stable conformations.