1r6u: Difference between revisions
New page: left|200px<br /> <applet load="1r6u" size="450" color="white" frame="true" align="right" spinBox="true" caption="1r6u, resolution 2.0Å" /> '''Crystal structure of... |
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[[Image:1r6u. | [[Image:1r6u.jpg|left|200px]]<br /><applet load="1r6u" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="1r6u, resolution 2.0Å" /> | caption="1r6u, resolution 2.0Å" /> | ||
'''Crystal structure of an active fragment of human tryptophanyl-tRNA synthetase with cytokine activity'''<br /> | '''Crystal structure of an active fragment of human tryptophanyl-tRNA synthetase with cytokine activity'''<br /> | ||
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==Overview== | ==Overview== | ||
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. | 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. | ||
==About this Structure== | ==About this Structure== | ||
1R6U is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with TYM and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Tryptophan--tRNA_ligase Tryptophan--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.2 6.1.1.2] Full crystallographic information is available from [http:// | 1R6U is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=TYM:'>TYM</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Tryptophan--tRNA_ligase Tryptophan--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.2 6.1.1.2] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1R6U OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: rossmann fold catalytic domain]] | [[Category: rossmann fold catalytic domain]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 13:48:39 2008'' | ||
Revision as of 14:48, 23 January 2008
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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.
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
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