Abstract
Arginyl-tRNA synthetase (ArgRS) is a tRNA-binding protein that catalyzes the esterification of l-arginine to its cognate tRNA. l-Canavanine, a structural analog of l-arginine, has recently been studied as an anticancer agent. Here, we determined the crystal structures of the apo, l-arginine-complexed, and l-canavanine-complexed forms of the cytoplasmic free isoform of human ArgRS (hArgRS). Similar interactions were formed upon binding to l-canavanine or l-arginine, but the interaction between Tyr312 and the oxygen of the oxyguanidino group was a little bit different. Detailed conformational changes that occur upon substrate binding were explained. The hArgRS structure was also compared with previously reported homologue structures. The results presented here may provide a basis for the design of new anticancer drugs, such as l-canavanine analogs.
Original language | English |
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Pages (from-to) | 2328-2334 |
Number of pages | 7 |
Journal | FEBS Letters |
Volume | 588 |
Issue number | 14 |
DOIs | |
Publication status | Published - 2014 Jun 27 |
Keywords
- Arginyl-tRNA synthetase
- Enzyme Commission number (6.1.1.19)
- Rossmann fold
- l-Arginine
- l-Canavanine
ASJC Scopus subject areas
- Biophysics
- Structural Biology
- Biochemistry
- Molecular Biology
- Genetics
- Cell Biology