title: Template-based structure prediction and molecular dynamics simulation study of two mammalian Aspartyl-tRNA synthetases.
abstract: 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 5ns 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.
authors.affiliation: Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan. zaheer.qasmi@iccs.edu
authors.forename: Zaheer
authors.initials: Z
authors.lastname: Ul-Haq
authors.forename: Waqasuddin
authors.initials: W
authors.lastname: Khan
authors.forename: Shamshad
authors.initials: S
authors.lastname: Zarina
authors.forename: Rabia
authors.initials: R
authors.lastname: Sattar
authors.forename: Syed Tarique
authors.initials: ST
authors.lastname: Moin
mesh_terms: D000818:Animals; D001226:Aspartate-tRNA Ligase / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D051379:Mice; D056004:Molecular Dynamics Simulation; D017433:Protein Structure, Secondary
chemical_list: D001226:Aspartate-tRNA Ligase