کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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443434 | 692722 | 2013 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: An in silico approach to evaluate the polyspecificity of methionyl-tRNA synthetases An in silico approach to evaluate the polyspecificity of methionyl-tRNA synthetases](/preview/png/443434.png)
Residue-specific incorporation is a technique used to replace natural amino acids with their close structural analogs, unnatural amino acids (UAAs), during protein synthesis. This is achieved by exploiting the substrate promiscuity of the wild type amino acyl tRNA synthetase (AARS) towards the close structural analogs of their cognate amino acids. In the past few decades, seleno-methionine was incorporated into proteins, using the substrate promiscuity of wild type AARSs, to resolve their crystal structures. Later, the incorporation of many UAAs showed that the AARSs are polyspecific to the close structural analogs of their cognate amino acids and that they maintain fidelity for the 19 natural amino acids. This polyspecificity helps to expand the use of this powerful tool to incorporate various UAA residues specifically through in vivo and in vitro approaches. Incorporation of UAAs is expensive, tedious and time-consuming. For the efficient incorporation of UAAs, it is important to screen substrate selectivity prior to their incorporation. As an initial study, using a docking tool, we analyzed the polyspecificity of the methionyl-tRNA synthetases (MetRSs) towards multiple reported and virtually generated methionine analogs. Based on the interaction result of these docking simulations, we predicted the substrate selectivity of the MetRS and the key residues responsible for the recognition of methionine analogs. Similarly, we compared the active site residues of the MetRSs of different species and identified the conserved amino acids in their active sites. Given the close similarity in the active site residues of these systems, we evaluated the polyspecificity of MetRSs.
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► Polyspecificity of E. coli and Yeast methionyl-tRNA synthetase (MetRS) was identified.
► Here, we reported the active site comparison of MetRS of different species.
► Novel substrates for MetRS were screened from Pubchem compound database.
► In silico analysis of MetRS substrate selectivity for reported and screened analogs.
► Identified novel MetRS substrates might help unnatural amino acid mutagenesis.
Journal: Journal of Molecular Graphics and Modelling - Volume 39, February 2013, Pages 79–86