1wka
From Proteopedia
(New page: 200px<br /><applet load="1wka" size="450" color="white" frame="true" align="right" spinBox="true" caption="1wka, resolution 1.70Å" /> '''Structural basis for...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1wka.gif|left|200px]]<br /><applet load="1wka" size=" | + | [[Image:1wka.gif|left|200px]]<br /><applet load="1wka" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1wka, resolution 1.70Å" /> | caption="1wka, resolution 1.70Å" /> | ||
'''Structural basis for non-cognate amino acid discrimination by the valyl-tRNA synthetase editing domain'''<br /> | '''Structural basis for non-cognate amino acid discrimination by the valyl-tRNA synthetase editing domain'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The editing domain of valyl-tRNA synthetase (ValRS) is known to deacylate, or edit, misformed Thr-tRNA(Val) (post-transfer editing). Here, we | + | The editing domain of valyl-tRNA synthetase (ValRS) is known to deacylate, or edit, misformed Thr-tRNA(Val) (post-transfer editing). Here, we determined the 1.7-Angstroms resolution crystal structure of the Thermus thermophilus ValRS editing domain. A comparison of the structure with the previously reported tRNA complex structure revealed conformational changes of the editing domain upon accommodation of the terminal A76; the "GTG loop" moves to expand the pocket, and the side chain of Phe-264 on the GTG loop rotates to interact with the A76 adenine ring. If these conformational changes did not occur, then C75 and A76 of the tRNA would clash with Phe-264. To elucidate the mechanism of the threonine side-chain recognition, we determined the crystal structure of the editing domain bound with [N-(L-threonyl)-sulfamoyl]adenosine at 1.7-Angstroms resolution. The gamma-OH of the threonyl moiety is recognized by the Lys-270, Thr-272, and Asp-279 side chains, which may reject the cognate valyl moiety. Accordingly, ValRS mutants with an Ala substitution for Lys-270 or Asp-279 synthesized significant amounts of Thr-tRNA(Val). The misproduced Thr-tRNA(Val) was hydrolyzed efficiently by the wild-type ValRS, but this post-transfer editing activity was drastically impaired by the Ala substitutions for Lys-270 and Asp-279 and was also decreased by those for Arg-216, Phe-264, and Thr-272. These results indicate that the threonyl moiety and A76 of Thr-tRNA(Val) are recognized by the Lys-270, Thr-272, and Asp-279 side chains and by the Phe-264 side chain, respectively, of the ValRS editing domain. |
==About this Structure== | ==About this Structure== | ||
| - | 1WKA is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Thermus_thermophilus Thermus thermophilus]. Active as [http://en.wikipedia.org/wiki/Valine--tRNA_ligase Valine--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.9 6.1.1.9] Full crystallographic information is available from [http:// | + | 1WKA is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Thermus_thermophilus Thermus thermophilus]. Active as [http://en.wikipedia.org/wiki/Valine--tRNA_ligase Valine--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.9 6.1.1.9] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WKA OCA]. |
==Reference== | ==Reference== | ||
| Line 15: | Line 15: | ||
[[Category: Valine--tRNA ligase]] | [[Category: Valine--tRNA ligase]] | ||
[[Category: Fukunaga, R.]] | [[Category: Fukunaga, R.]] | ||
| - | [[Category: RSGI, RIKEN | + | [[Category: RSGI, RIKEN Structural Genomics/Proteomics Initiative.]] |
[[Category: Yokoyama, S.]] | [[Category: Yokoyama, S.]] | ||
[[Category: amino acid]] | [[Category: amino acid]] | ||
| Line 28: | Line 28: | ||
[[Category: valyl-trna synthetase]] | [[Category: valyl-trna synthetase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:45:17 2008'' |
Revision as of 13:45, 21 February 2008
|
Structural basis for non-cognate amino acid discrimination by the valyl-tRNA synthetase editing domain
Overview
The editing domain of valyl-tRNA synthetase (ValRS) is known to deacylate, or edit, misformed Thr-tRNA(Val) (post-transfer editing). Here, we determined the 1.7-Angstroms resolution crystal structure of the Thermus thermophilus ValRS editing domain. A comparison of the structure with the previously reported tRNA complex structure revealed conformational changes of the editing domain upon accommodation of the terminal A76; the "GTG loop" moves to expand the pocket, and the side chain of Phe-264 on the GTG loop rotates to interact with the A76 adenine ring. If these conformational changes did not occur, then C75 and A76 of the tRNA would clash with Phe-264. To elucidate the mechanism of the threonine side-chain recognition, we determined the crystal structure of the editing domain bound with [N-(L-threonyl)-sulfamoyl]adenosine at 1.7-Angstroms resolution. The gamma-OH of the threonyl moiety is recognized by the Lys-270, Thr-272, and Asp-279 side chains, which may reject the cognate valyl moiety. Accordingly, ValRS mutants with an Ala substitution for Lys-270 or Asp-279 synthesized significant amounts of Thr-tRNA(Val). The misproduced Thr-tRNA(Val) was hydrolyzed efficiently by the wild-type ValRS, but this post-transfer editing activity was drastically impaired by the Ala substitutions for Lys-270 and Asp-279 and was also decreased by those for Arg-216, Phe-264, and Thr-272. These results indicate that the threonyl moiety and A76 of Thr-tRNA(Val) are recognized by the Lys-270, Thr-272, and Asp-279 side chains and by the Phe-264 side chain, respectively, of the ValRS editing domain.
About this Structure
1WKA is a Single protein structure of sequence from Thermus thermophilus. Active as Valine--tRNA ligase, with EC number 6.1.1.9 Full crystallographic information is available from OCA.
Reference
Structural basis for non-cognate amino acid discrimination by the valyl-tRNA synthetase editing domain., Fukunaga R, Yokoyama S, J Biol Chem. 2005 Aug 19;280(33):29937-45. Epub 2005 Jun 21. PMID:15970591
Page seeded by OCA on Thu Feb 21 15:45:17 2008
Categories: Single protein | Thermus thermophilus | Valine--tRNA ligase | Fukunaga, R. | RSGI, RIKEN Structural Genomics/Proteomics Initiative. | Yokoyama, S. | Amino acid | Cp1 | Editing | Fidelity | Riken structural genomics/proteomics initiative | Rsgi | Structural genomics | Thermus thrmophilus | Translation | Valyl-trna synthetase
