Post-transfer editing by a eukaryotic leucyl-tRNA synthetase resistant to the broad-spectrum drug AN2690
文献类型：期刊论文
| 作者 | Zhou, XL; Tan, M; Wang, M; Chen, X; Wang, ED |
| 刊名 | BIOCHEMICAL JOURNAL
 |
| 出版日期 | 2010 |
| 卷号 | 430期号:1页码:325-333 |
| 关键词 | connective peptide 1 domain (CP1 domain) editing eukarya-specific insertion 1 (ESI) Giardia lamblia leucyl-tRNA synthetase |
| 通讯作者 | Wang, ED (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, 320 Yue Yang Rd, Shanghai 200031, Peoples R China.,edwang@sibs.ac.cn |
| 英文摘要 | Some aaRSs (aminoacyl-tRNA synthetases) develop editing mechanisms to correct mis-charged tRNA. The CP1 (connective peptide 1) domain of LeuRS (leucyl-tRNA synthetase) contains the editing active site, which is the proven target for the broad-spectrum drug AN2690 (5-fluoro-1,3-dihydro-l-hydroxy-2,1-benzoxaborole). The ESI (eukarya-specific insertion 1) in the CP1 domain of G/LeuRS (Giardia lamblia LeuRS) has been identified. Similar substitution with the ESI from HsLeuRS (Homo sapiens LeuRS) impeded the leucine activation, aminoacylation and post-transfer editing of the enzyme, but had no effect on the editing specificity toward non-specific amino acids. The(341) in G/LeuRS served as a specificity discriminator, as found in other LeuRS systems, although its substitution with an alanine residue did not destroy Leu-tRNA(Leu) synthesis in vitro and in vivo. The Arg(338) was crucial for tRNA(Leu) charging and the Asp(440) was crucial for leucine activation and aminoacylation. The post-transfer editing required the CTD (C-terminal domain), Arg(338) and Asp(440) of G/LeuRS. Interestingly, G/LeuRS was completely resistant to the AN2690, which is an inhibitor of various LeuRSs. The universally conserved aspartate residue in the LeuRS CP1 domains was responsible for the resistance of G/LeuRS and another recently reported AN2690-resistant AaLeuRS (Aquifex aeolicus LeuRS). Our results indicate the functional divergence of some absolutely conserved sites, improve the understanding of the editing function of eukaryotic/archaeal LeuRSs and shed light on the development of a G/LeuRS-specific inhibitor for the treatment of giardiasis. |
| 学科主题 | Biochemistry & Molecular Biology |
| 类目[WOS] | Biochemistry & Molecular Biology |
| 关键词[WOS] | STRUCTURAL BASIS ; GIARDIA-LAMBLIA ; CRYSTAL-STRUCTURES ; CELL VIABILITY ; CP1 DOMAIN ; L-VALINE ; DISCRIMINATION ; TRNA(LEU) ; COMPLEX ; THREONINE |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000281490200016 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/1110]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Zhou, XL,Tan, M,Wang, M,et al. Post-transfer editing by a eukaryotic leucyl-tRNA synthetase resistant to the broad-spectrum drug AN2690[J]. BIOCHEMICAL JOURNAL,2010,430(1):325-333. |
| APA | Zhou, XL,Tan, M,Wang, M,Chen, X,&Wang, ED.(2010).Post-transfer editing by a eukaryotic leucyl-tRNA synthetase resistant to the broad-spectrum drug AN2690.BIOCHEMICAL JOURNAL,430(1),325-333. |
| MLA | Zhou, XL,et al."Post-transfer editing by a eukaryotic leucyl-tRNA synthetase resistant to the broad-spectrum drug AN2690".BIOCHEMICAL JOURNAL 430.1(2010):325-333. |
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