Reassignment of sense codons: Designing and docking of proline analogs for Escherichia coli prolyl-tRNA synthetase to expand the genetic code
- Reassignment of sense codons: Designing and docking of proline analogs for Escherichia coli prolyl-tRNA synthetase to expand the genetic code
- 윤형돈; 나다라잔사라바난[나다라잔사라바난]; 니라이쿨람아야두레이; 카나가벨디판쿠마[카나가벨디판쿠마]; 정태완; 임동준
- UNNATURAL AMINO-ACIDS; PROTEINS; TOOLS
- Issue Date
- ELSEVIER SCIENCE BV
- JOURNAL OF MOLECULAR CATALYSIS B-ENZYMATIC, v.78, pp.57 - 64
- Amino acyl-tRNA synthetases (AARSs) play a vital role in protein synthesis by catalyzing the aminoacylation of tRNA with its cognate amino acid. More recently, the endogenous AARS has been reported to recognize the close structural analogs of its cognate amino acid and helps in the in vitro and in vivo incorporation of analogs into recombinant proteins. By exploiting this substrate promiscuity, a number of non-canonical amino acids were successfully incorporated into the recombinant proteins. However, the incorporation efficiency varies with the different structural analogs depending on their reactivity towards the tRNA synthetases, which is due to the interaction and accommodation in the active site. Here, to analyze the incorporation efficiency of different praline analogs and to predict the active site residues responsible for the recognition, we carried out molecular docking study with the modeled Escherchia coli prolyl-tRNA synthetase (EcProRS). We also mapped the binding mode for the reported, virtually generated proline analogs and compared it with the reported crystal structure. The reactivity of the reported analogs was correlated with the biochemical data with respect to their interaction and orientation in the active site, which demonstrates the role of active site residues for the recognition of proline analogs and some new substrates such as chloro, bromo and iodoproline for EcProRS. We also rationally designed a EcProRS mutant for desired proline analog and validated by docking simulation with 3D model structure. (C) 2012 Elsevier B.V. All rights reserved.
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