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| | ==Crystal structures of human tryptophanyl-tRNA synthetase in complex with ATP(putative)== | | ==Crystal structures of human tryptophanyl-tRNA synthetase in complex with ATP(putative)== |
| - | <StructureSection load='2quk' size='340' side='right' caption='[[2quk]], [[Resolution|resolution]] 2.80Å' scene=''> | + | <StructureSection load='2quk' size='340' side='right'caption='[[2quk]], [[Resolution|resolution]] 2.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2quk]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QUK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2QUK FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2quk]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QUK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QUK FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1o5t|1o5t]], [[2ake|2ake]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">WARS, IFI53, WRS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2quk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2quk OCA], [https://pdbe.org/2quk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2quk RCSB], [https://www.ebi.ac.uk/pdbsum/2quk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2quk ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr>
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| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2quk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2quk OCA], [http://pdbe.org/2quk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2quk RCSB], [http://www.ebi.ac.uk/pdbsum/2quk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2quk ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SYWC_HUMAN SYWC_HUMAN]] Isoform 1, isoform 2 and T1-TrpRS have aminoacylation activity while T2-TrpRS lacks it. Isoform 2, T1-TrpRS and T2-TrpRS possess angiostatic activity whereas isoform 1 lacks it. T2-TrpRS inhibits fluid shear stress-activated responses of endothelial cells. Regulates ERK, Akt, and eNOS activation pathways that are associated with angiogenesis, cytoskeletal reorganization and shear stress-responsive gene expression.<ref>PMID:11773626</ref> <ref>PMID:1373391</ref> <ref>PMID:11773625</ref> <ref>PMID:14630953</ref> | + | [https://www.uniprot.org/uniprot/SYWC_HUMAN SYWC_HUMAN] Isoform 1, isoform 2 and T1-TrpRS have aminoacylation activity while T2-TrpRS lacks it. Isoform 2, T1-TrpRS and T2-TrpRS possess angiostatic activity whereas isoform 1 lacks it. T2-TrpRS inhibits fluid shear stress-activated responses of endothelial cells. Regulates ERK, Akt, and eNOS activation pathways that are associated with angiogenesis, cytoskeletal reorganization and shear stress-responsive gene expression.<ref>PMID:11773626</ref> <ref>PMID:1373391</ref> <ref>PMID:11773625</ref> <ref>PMID:14630953</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | ==See Also== | | ==See Also== |
| - | *[[Aminoacyl tRNA Synthetase|Aminoacyl tRNA Synthetase]] | + | *[[Aminoacyl tRNA synthetase 3D structures|Aminoacyl tRNA synthetase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Tryptophan--tRNA ligase]] | + | [[Category: Large Structures]] |
| - | [[Category: Ding, J P]] | + | [[Category: Ding JP]] |
| - | [[Category: Shen, N]] | + | [[Category: Shen N]] |
| - | [[Category: Aminoacyl-trna synthetase]]
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| - | [[Category: Atp-binding]]
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| - | [[Category: Cytoplasm]]
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| - | [[Category: Induced-fit mechnism]]
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| - | [[Category: Ligase]]
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| - | [[Category: Nucleotide-binding]]
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| - | [[Category: Protein biosynthesis]]
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| - | [[Category: Rossmann fold]]
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| Structural highlights
Function
SYWC_HUMAN Isoform 1, isoform 2 and T1-TrpRS have aminoacylation activity while T2-TrpRS lacks it. Isoform 2, T1-TrpRS and T2-TrpRS possess angiostatic activity whereas isoform 1 lacks it. T2-TrpRS inhibits fluid shear stress-activated responses of endothelial cells. Regulates ERK, Akt, and eNOS activation pathways that are associated with angiogenesis, cytoskeletal reorganization and shear stress-responsive gene expression.[1] [2] [3] [4]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Human tryptophanyl-tRNA synthetase (hTrpRS) differs from its bacterial counterpart at several key positions of the catalytic active site and has an extra N-terminal domain, implying possibly a different catalytic mechanism. We report here the crystal structures of hTrpRS in complexes with Trp, tryptophanamide and ATP and tryptophanyl-AMP, respectively, which represent three different enzymatic states of the Trp activation reaction. Analyses of these structures reveal the molecular basis of the mechanisms of the substrate recognition and the activation reaction. The dimeric hTrpRS is structurally and functionally asymmetric with half-of-the-sites reactivity. Recognition of Trp is by an induced-fit mechanism involving conformational change of the AIDQ motif that creates a perfect pocket for the binding and activation of Trp and causes coupled movements of the N-terminal and C-terminal domains. The KMSAS loop appears to have an inherent flexibility and the binding of ATP stabilizes it in a closed conformation that secures the position of ATP for catalysis. Our structural data indicate that the catalytic mechanism of the Trp activation reaction by hTrpRS involves more moderate conformational changes of the structural elements at the active site to recognize and bind the substrates, which is more complex and fine-tuned than that of bacterial TrpRS.
Catalytic mechanism of the tryptophan activation reaction revealed by crystal structures of human tryptophanyl-tRNA synthetase in different enzymatic states.,Shen N, Zhou M, Yang B, Yu Y, Dong X, Ding J Nucleic Acids Res. 2008 Mar;36(4):1288-99. Epub 2008 Jan 7. PMID:18180246[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Wakasugi K, Slike BM, Hood J, Otani A, Ewalt KL, Friedlander M, Cheresh DA, Schimmel P. A human aminoacyl-tRNA synthetase as a regulator of angiogenesis. Proc Natl Acad Sci U S A. 2002 Jan 8;99(1):173-7. Epub 2002 Jan 2. PMID:11773626 doi:10.1073/pnas.012602099
- ↑ Bange FC, Flohr T, Buwitt U, Bottger EC. An interferon-induced protein with release factor activity is a tryptophanyl-tRNA synthetase. FEBS Lett. 1992 Mar 30;300(2):162-6. PMID:1373391
- ↑ Otani A, Slike BM, Dorrell MI, Hood J, Kinder K, Ewalt KL, Cheresh D, Schimmel P, Friedlander M. A fragment of human TrpRS as a potent antagonist of ocular angiogenesis. Proc Natl Acad Sci U S A. 2002 Jan 8;99(1):178-83. Epub 2002 Jan 2. PMID:11773625 doi:10.1073/pnas.012601899
- ↑ Tzima E, Reader JS, Irani-Tehrani M, Ewalt KL, Schwartz MA, Schimmel P. Biologically active fragment of a human tRNA synthetase inhibits fluid shear stress-activated responses of endothelial cells. Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):14903-7. Epub 2003 Nov 20. PMID:14630953 doi:10.1073/pnas.2436330100
- ↑ Shen N, Zhou M, Yang B, Yu Y, Dong X, Ding J. Catalytic mechanism of the tryptophan activation reaction revealed by crystal structures of human tryptophanyl-tRNA synthetase in different enzymatic states. Nucleic Acids Res. 2008 Mar;36(4):1288-99. Epub 2008 Jan 7. PMID:18180246 doi:http://dx.doi.org/10.1093/nar/gkm1153
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