1r6u: Difference between revisions
No edit summary |
No edit summary |
||
| Line 4: | Line 4: | ||
==Overview== | ==Overview== | ||
Higher eukaryote tRNA synthetases have expanded functions that come from | Higher eukaryote tRNA synthetases have expanded functions that come from enlarged, more differentiated structures that were adapted to fit aminoacylation function. How those adaptations affect catalytic mechanisms is not known. Presented here is the structure of a catalytically active natural splice variant of human tryptophanyl-tRNA synthetase (TrpRS) that is a potent angiostatic factor. This and related structures suggest that a eukaryote-specific N-terminal extension of the core enzyme changed substrate recognition by forming an active site cap. At the junction of the extension and core catalytic unit, an arginine is recruited to replace a missing landmark lysine almost 200 residues away. Mutagenesis, rapid kinetic, and substrate binding studies support the functional significance of the cap and arginine recruitment. Thus, the enzyme function of human TrpRS has switched more to the N terminus of the sequence. This switch has the effect of creating selective pressure to retain the N-terminal extension for functional expansion. | ||
==Disease== | |||
Known disease associated with this structure: Wolcott-Rallison syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=604032 604032]] | |||
==About this Structure== | ==About this Structure== | ||
| Line 14: | Line 17: | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Tryptophan--tRNA ligase]] | [[Category: Tryptophan--tRNA ligase]] | ||
[[Category: McRee, D | [[Category: McRee, D E.]] | ||
[[Category: Otero, F | [[Category: Otero, F J.]] | ||
[[Category: Pouplana, L | [[Category: Pouplana, L Ribas de.]] | ||
[[Category: Schimmel, P.]] | [[Category: Schimmel, P.]] | ||
[[Category: Skene, R | [[Category: Skene, R J.]] | ||
[[Category: Yang, X | [[Category: Yang, X L.]] | ||
[[Category: GOL]] | [[Category: GOL]] | ||
[[Category: TYM]] | [[Category: TYM]] | ||
| Line 27: | Line 30: | ||
[[Category: rossmann fold catalytic domain]] | [[Category: rossmann fold catalytic domain]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:47:42 2008'' | ||
Revision as of 15:47, 21 February 2008
|
Crystal structure of an active fragment of human tryptophanyl-tRNA synthetase with cytokine activity
OverviewOverview
Higher eukaryote tRNA synthetases have expanded functions that come from enlarged, more differentiated structures that were adapted to fit aminoacylation function. How those adaptations affect catalytic mechanisms is not known. Presented here is the structure of a catalytically active natural splice variant of human tryptophanyl-tRNA synthetase (TrpRS) that is a potent angiostatic factor. This and related structures suggest that a eukaryote-specific N-terminal extension of the core enzyme changed substrate recognition by forming an active site cap. At the junction of the extension and core catalytic unit, an arginine is recruited to replace a missing landmark lysine almost 200 residues away. Mutagenesis, rapid kinetic, and substrate binding studies support the functional significance of the cap and arginine recruitment. Thus, the enzyme function of human TrpRS has switched more to the N terminus of the sequence. This switch has the effect of creating selective pressure to retain the N-terminal extension for functional expansion.
DiseaseDisease
Known disease associated with this structure: Wolcott-Rallison syndrome OMIM:[604032]
About this StructureAbout this Structure
1R6U is a Single protein structure of sequence from Homo sapiens with and as ligands. Active as Tryptophan--tRNA ligase, with EC number 6.1.1.2 Full crystallographic information is available from OCA.
ReferenceReference
Functional and crystal structure analysis of active site adaptations of a potent anti-angiogenic human tRNA synthetase., Yang XL, Guo M, Kapoor M, Ewalt KL, Otero FJ, Skene RJ, McRee DE, Schimmel P, Structure. 2007 Jul;15(7):793-805. PMID:17637340
Page seeded by OCA on Thu Feb 21 14:47:42 2008