Molecular dynamics simulation study of valyl-tRNA synthetase with its pre- and post-transfer editing substrates
| Autor: | Keun Woo Lee, Kavitha Bharatham, Nagakumar Bharatham, Yuno Lee |
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| Rok vydání: | 2009 |
| Předmět: |
Models
Molecular Threonine Protein Conformation Valine-tRNA Ligase Biophysics Substrate analog Biochemistry Substrate Specificity Molecular dynamics chemistry.chemical_compound RNA Transfer Point Mutation Computer Simulation chemistry.chemical_classification Aspartic Acid Lysine Thermus thermophilus Point mutation Organic Chemistry Valine Adenosine Monophosphate Amino acid Valyl-tRNA synthetase chemistry Transfer RNA Proofreading Protein Binding |
| Zdroj: | Biophysical Chemistry. 143:34-43 |
| ISSN: | 0301-4622 |
| DOI: | 10.1016/j.bpc.2009.03.009 |
| Popis: | The main role of aminoacyl-tRNA synthetases (aaRSs) is to transfer the cognate amino acids to the 3'-end of their tRNA by strictly discriminating from non-cognate amino acids. Some aaRSs accomplish this via proofreading and editing mechanisms, among which valyl-tRNA synthetase (ValRS) hydrolyses the non-cognate amino acid, threonine. In ValRS, existence of pre-transfer editing process is still unclear, although crystal structure of editing site with pre-transfer substrate analog (Thr-AMS) was released. In the case of isoleucyl-tRNA synthetase (IleRS), editing mechanism is well studied and mutational analyses revealed the existence of post- and pre-transfer editing mechanisms. Our aim is to investigate the possibility of pre-transfer editing process by performing molecular dynamics (MD) simulation studies. Simulations were carried out for ValRS with pre-transfer substrates (Thr-AMP/Val-AMP) and post-transfer substrates (Thr-A76/Val-A76) to understand their binding pattern. Two important point mutation studies were performed to observe their effect on editing process. This study also intends to compare and contrast the pre-transfer editing with post-transfer editing of ValRS. Interestingly, the MD simulation results revealed that non-cognate substrates (Thr-AMP/Thr-A76) bind more strongly than the cognate substrates (Val-AMP/Val-A76) in both pre- and post-transfer editing respectively. The editing site mutations (Lys270Ala and Asp279Ala) severely affected the binding ability of pre-transfer substrate (Thr-AMP) by different ways. Even though pre- and post-transfer substrates bind to the same site, specific differences were observed which has led us to believe the existence of the pre-transfer editing process in ValRS. |
| Databáze: | OpenAIRE |
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