View source for 4ttv


==Crystal structure of human ThrRS complexing with a bioengineered macrolide BC194==
<StructureSection load='4ttv' size='340' side='right'caption='[[4ttv]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4ttv]] is a 4 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=4TTV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4TTV FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BC9:(1R,2R)-2-[(2S,6E,8R,9S,11R,13S,15S,16S)-7-CYANO-8,16-DIHYDROXY-9,11,13,15-TETRAMETHYL-18-OXOOXACYCLOOCTADEC-6-EN-2-YL]CYCLOBUTANECARBOXYLIC+ACID'>BC9</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=4ttv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ttv OCA], [https://pdbe.org/4ttv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ttv RCSB], [https://www.ebi.ac.uk/pdbsum/4ttv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ttv ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SYTC_HUMAN SYTC_HUMAN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Aminoacyl-tRNA synthetases (AARSs) catalyze an early step in protein synthesis, but also regulate diverse physiological processes in animal cells. These include angiogenesis, and human threonyl-tRNA synthetase (TARS) represents a potent pro-angiogenic AARS. Angiogenesis stimulation can be blocked by the macrolide antibiotic borrelidin (BN), which exhibits a broad spectrum toxicity that has discouraged deeper investigation. Recently, a less toxic variant (BC194) was identified that potently inhibits angiogenesis. Employing biochemical, cell biological, and biophysical approaches, we demonstrate that the toxicity of BN and its derivatives is linked to its competition with the threonine substrate at the molecular level, which stimulates amino acid starvation and apoptosis. By separating toxicity from the inhibition of angiogenesis, a direct role for TARS in vascular development in the zebrafish could be demonstrated. Bioengineered natural products are thus useful tools in unmasking the cryptic functions of conventional enzymes in the regulation of complex processes in higher metazoans.

Aminoacyl-tRNA synthetase dependent angiogenesis revealed by a bioengineered macrolide inhibitor.,Mirando AC, Fang P, Williams TF, Baldor LC, Howe AK, Ebert AM, Wilkinson B, Lounsbury KM, Guo M, Francklyn CS Sci Rep. 2015 Aug 14;5:13160. doi: 10.1038/srep13160. PMID:26271225<ref>PMID:26271225</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4ttv" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Fang P]]
[[Category: Guo M]]