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3q4t
From Proteopedia
(Difference between revisions)
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| - | + | ==Crystal structure of Activin receptor type-IIA (ACVR2A) kinase domain in complex with dorsomorphin== | |
| - | + | <StructureSection load='3q4t' size='340' side='right' caption='[[3q4t]], [[Resolution|resolution]] 1.96Å' scene=''> | |
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[3q4t]] is a 2 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=3Q4T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3Q4T FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TAK:6-[4-(2-PIPERIDIN-1-YLETHOXY)PHENYL]-3-PYRIDIN-4-YLPYRAZOLO[1,5-A]PYRIMIDINE'>TAK</scene></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ACVR2, ACVR2A ([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/Receptor_protein_serine/threonine_kinase Receptor protein serine/threonine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.30 2.7.11.30] </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=3q4t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3q4t OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3q4t RCSB], [http://www.ebi.ac.uk/pdbsum/3q4t PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | GDF8, or myostatin, is a member of the TGF-beta superfamily of secreted polypeptide growth factors. GDF8 is a potent negative regulator of myogenesis both in vivo and in vitro. We found that GDF8 signaling was inhibited by the small molecule ATP competitive inhibitors Dorsomorphin and LDN-193189. These compounds were previously shown to be potent inhibitors of BMP signaling by binding to the type BMP type I receptors ALK1/2/3/6. We present the crystal structure of the type II receptor ActRIIA with dorsomorphin, and demonstrate that dorsomorphin or LDN-193189 target GDF8 induced Smad2/3 signaling and repression of myogenic transcription factors. As a result, both inhibitors rescue myogenesis in myoblasts treated with GDF8. As revealed by quantitative live cell microscopy, treatment with dorsomorphin or LDN-193189 promoted the contractile activity of myotubular networks in vitro. We therefore suggest these inhibitors as suitable tools to promote functional myogenesis. | ||
| - | + | Small Molecules Dorsomorphin and LDN-193189 Inhibit Myostatin/GDF8 Signaling and Promote Functional Myoblast Differentiation.,Horbelt D, Boergermann JH, Chaikuad A, Alfano I, Williams E, Lukonin I, Timmel T, Bullock AN, Knaus P J Biol Chem. 2014 Nov 3. pii: jbc.M114.604397. PMID:25368322<ref>PMID:25368322</ref> | |
| - | + | ||
| - | [[Category: | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| + | </div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Human]] | ||
[[Category: Receptor protein serine/threonine kinase]] | [[Category: Receptor protein serine/threonine kinase]] | ||
| - | [[Category: Alfano, I | + | [[Category: Alfano, I]] |
| - | [[Category: Arrowsmith, C H | + | [[Category: Arrowsmith, C H]] |
| - | [[Category: Bountra, C | + | [[Category: Bountra, C]] |
| - | [[Category: Bullock, A | + | [[Category: Bullock, A]] |
| - | [[Category: Chaikuad, A | + | [[Category: Chaikuad, A]] |
| - | [[Category: Cooper, C D.O | + | [[Category: Cooper, C D.O]] |
| - | [[Category: Delft, F von | + | [[Category: Delft, F von]] |
| - | [[Category: Edwards, A M | + | [[Category: Edwards, A M]] |
| - | [[Category: Krojer, T | + | [[Category: Krojer, T]] |
| - | [[Category: Mahajan, P | + | [[Category: Mahajan, P]] |
| - | [[Category: Muniz, J R.C | + | [[Category: Muniz, J R.C]] |
| - | [[Category: Raynor, J | + | [[Category: Raynor, J]] |
| - | [[Category: | + | [[Category: Structural genomic]] |
| - | [[Category: Sanvitale, C | + | [[Category: Sanvitale, C]] |
| - | [[Category: Vollmar, M | + | [[Category: Vollmar, M]] |
| - | [[Category: Weigelt, J | + | [[Category: Weigelt, J]] |
[[Category: Protein kinase]] | [[Category: Protein kinase]] | ||
[[Category: Sgc]] | [[Category: Sgc]] | ||
| - | [[Category: Structural genomics consortium]] | ||
[[Category: Transferase]] | [[Category: Transferase]] | ||
Revision as of 11:52, 10 December 2014
Crystal structure of Activin receptor type-IIA (ACVR2A) kinase domain in complex with dorsomorphin
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Categories: Human | Receptor protein serine/threonine kinase | Alfano, I | Arrowsmith, C H | Bountra, C | Bullock, A | Chaikuad, A | Cooper, C D.O | Delft, F von | Edwards, A M | Krojer, T | Mahajan, P | Muniz, J R.C | Raynor, J | Structural genomic | Sanvitale, C | Vollmar, M | Weigelt, J | Protein kinase | Sgc | Transferase
