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3bum
From Proteopedia
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| - | {{Seed}} | ||
| - | [[Image:3bum.png|left|200px]] | ||
| - | + | ==Crystal structure of c-Cbl-TKB domain complexed with its binding motif in Sprouty2== | |
| - | + | <StructureSection load='3bum' size='340' side='right'caption='[[3bum]], [[Resolution|resolution]] 2.00Å' scene=''> | |
| - | You may | + | == Structural highlights == |
| - | + | <table><tr><td colspan='2'>[[3bum]] is a 2 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=3BUM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BUM FirstGlance]. <br> | |
| - | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> | |
| - | -- | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</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=3bum FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bum OCA], [https://pdbe.org/3bum PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3bum RCSB], [https://www.ebi.ac.uk/pdbsum/3bum PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3bum ProSAT]</span></td></tr> | |
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/SPY2_HUMAN SPY2_HUMAN] May function as an antagonist of fibroblast growth factor (FGF) pathways and may negatively modulate respiratory organogenesis.<ref>PMID:10887178</ref> | ||
| + | == Evolutionary Conservation == | ||
| + | [[Image:Consurf_key_small.gif|200px|right]] | ||
| + | Check<jmol> | ||
| + | <jmolCheckbox> | ||
| + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bu/3bum_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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/main_output.php?pdb_ID=3bum ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The c-Cbl tyrosine kinase binding domain (Cbl-TKB), essentially an 'embedded' SH2 domain, has a critical role in targeting proteins for ubiquitination. To address how this domain can bind to disparate recognition mofits and to determine whether this results in variations in substrate-binding affinity, we compared crystal structures of the Cbl-TKB domain complexed with phosphorylated peptides of Sprouty2, Sprouty4, epidermal growth factor receptor, Syk, and c-Met receptors and validated the binding with point-mutational analyses using full-length proteins. An obligatory, intrapeptidyl H-bond between the phosphotyrosine and the conserved asparagine or adjacent arginine is essential for binding and orients the peptide into a positively charged pocket on c-Cbl. Surprisingly, c-Met bound to Cbl in the reverse direction, which is unprecedented for SH2 domain binding. The necessity of this intrapeptidyl H-bond was confirmed with isothermal titration calorimetry experiments that also showed Sprouty2 to have the highest binding affinity to c-Cbl; this may enable the selective sequestration of c-Cbl from other target proteins. | ||
| - | + | Structural basis for a novel intrapeptidyl H-bond and reverse binding of c-Cbl-TKB domain substrates.,Ng C, Jackson RA, Buschdorf JP, Sun Q, Guy GR, Sivaraman J EMBO J. 2008 Mar 5;27(5):804-16. Epub 2008 Feb 14. PMID:18273061<ref>PMID:18273061</ref> | |
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 3bum" style="background-color:#fffaf0;"></div> | ||
| - | + | ==See Also== | |
| - | + | *[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]] | |
| - | + | == References == | |
| - | + | <references/> | |
| - | + | __TOC__ | |
| - | + | </StructureSection> | |
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: Buschdorf | + | [[Category: Buschdorf PJ]] |
| - | [[Category: Guy | + | [[Category: Guy RG]] |
| - | [[Category: Jackson | + | [[Category: Jackson AR]] |
| - | [[Category: Ng | + | [[Category: Ng C]] |
| - | [[Category: Sivaraman | + | [[Category: Sivaraman J]] |
| - | [[Category: Sun | + | [[Category: Sun Q]] |
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Current revision
Crystal structure of c-Cbl-TKB domain complexed with its binding motif in Sprouty2
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Categories: Homo sapiens | Large Structures | Buschdorf PJ | Guy RG | Jackson AR | Ng C | Sivaraman J | Sun Q

