2quh

From Proteopedia

(Difference between revisions)

Revision as of 11:12, 5 September 2018

Crystal structures of human tryptophanyl-tRNA synthetase in complex with Trp

Structural highlights

2quh is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	1o5t, 2ake
Gene:	WARS, IFI53, WRS (HUMAN)
Activity:	Tryptophan--tRNA ligase, with EC number 6.1.1.2
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

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

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2quh"

@@ Line 1: / Line 1: @@
 ==Crystal structures of human tryptophanyl-tRNA synthetase in complex with Trp==
 <StructureSection load='2quh' size='340' side='right' caption='[[2quh]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
@@ Line 7: / Line 8: @@
 <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='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>
-<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=2quh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2quh OCA], [http://pdbe.org/2quh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2quh RCSB], [http://www.ebi.ac.uk/pdbsum/2quh PDBsum]</span></td></tr>
+<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=2quh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2quh OCA], [http://pdbe.org/2quh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2quh RCSB], [http://www.ebi.ac.uk/pdbsum/2quh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2quh ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 15: / Line 16: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/qu/2quh_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/qu/2quh_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
-</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2quh ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 43: / Line 44: @@
 [[Category: Aminoacyl-trna synthetase]]
 [[Category: Atp-binding]]
+[[Category: Cytoplasm]]
 [[Category: Induced-fit mechnism]]
 [[Category: Ligase]]

2quh

From Proteopedia

Revision as of 11:12, 5 September 2018

Crystal structures of human tryptophanyl-tRNA synthetase in complex with Trp

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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