ePrints@IIScePrints@IISc Home | About | Browse | Latest Additions | Advanced Search | Contact | Help

Ligand dependent intra and inter subunit communication in human tryptophanyl tRNA synthetase as deduced from the dynamics of structure networks

Hansia, Priti and Ghosh, Amit and Vishveshwara, Saraswathi (2009) Ligand dependent intra and inter subunit communication in human tryptophanyl tRNA synthetase as deduced from the dynamics of structure networks. In: Molecular biosystems, 5 (12). pp. 1860-1872.

[img] PDF
9.pdf - Published Version
Restricted to Registered users only

Download (2979Kb) | Request a copy
Official URL: http://www.rsc.org/Publishing/Journals/MB/article....

Abstract

Homodimeric protein tryptophanyl tRNA synthetase (TrpRS) has a Rossmann fold domain and belongs to the 1c subclass of aminoacyl tRNA synthetases. This enzyme performs the function of acylating the cognate tRNA. This process involves a number of molecules (2 protein subunits, 2 tRNAs and 2 activated Trps) and thus it is difficult to follow the complex steps in this process. Structures of human TrpRS complexed with certain ligands are available. Based on structural and biochemical data, mechanism of activation of Trp has been speculated. However, no structure has yet been solved in the presence of both the tRNA(Trp) and the activated Trp (TrpAMP). In this study, we have modeled the structure of human TrpRS bound to the activated ligand and the cognate tRNA. In addition, we have performed molecular dynamics (MD) simulations on these models as well as other complexes to capture the dynamical process of ligand induced conformational changes. We have analyzed both the local and global changes in the protein conformation from the protein structure network (PSN) of MD snapshots, by a method which was recently developed in our laboratory in the context of the functionally monomeric protein, methionyl tRNA synthetase. From these investigations, we obtain important information such as the ligand induced correlation between different residues of this protein, asymmetric binding of the ligands to the two subunits of the protein as seen in the crystal structure analysis, and the path of communication between the anticodon region and the aminoacylation site. Here we are able to elucidate the role of dimer interface at a level of detail, which has not been captured so far.

Item Type: Journal Article
Additional Information: Copyright for this article belongs to Royal Society of Chemistry.
Department/Centre: Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited: 03 Dec 2009 04:57
Last Modified: 19 Sep 2010 05:53
URI: http://eprints.iisc.ernet.in/id/eprint/25054

Actions (login required)

View Item View Item