View source for 2jyq


==NMR structure of the apo v-Src SH2 domain==
<StructureSection load='2jyq' size='340' side='right'caption='[[2jyq]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2jyq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Rous_sarcoma_virus Rous sarcoma virus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JYQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JYQ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2jyq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jyq OCA], [https://pdbe.org/2jyq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jyq RCSB], [https://www.ebi.ac.uk/pdbsum/2jyq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jyq ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SRC_RSVSE SRC_RSVSE] This phosphoprotein, required for both the initiation and the maintenance of neoplastic transformation, is a protein kinase that catalyzes the phosphorylation of tyrosine residues in vitro (By similarity).
== 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/jy/2jyq_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/main_output.php?pdb_ID=2jyq ConSurf].
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== Publication Abstract from PubMed ==
SH2 domains provide fundamental recognition sites in tyrosine kinase-mediated signaling pathways which, when aberrant, give rise to disease states such as cancer, diabetes, and immune deficiency. Designing specific inhibitors that target the SH2 domain-binding site, however, have presented a major challenge. Despite well over a decade of intensive research, clinically useful SH2 domain inhibitors have yet to become available. A better understanding of the structural, dynamic, and thermodynamic contributions to ligand binding of individual SH2 domains will provide some insight as to whether inhibitor development is possible. We report the first high resolution solution structure of the apo-v-Src SH2 domain. This is accompanied by the analysis of backbone dynamics and pK(a) values within the apo- and peptide-bound states. Our results indicate that the phosphotyrosine (pY) pocket is tightly structured and hence not adaptable to exogenous ligands. On the other hand, the pocket which accommodates residues proximal and C-terminal of the pY (pY + 3) or so-called specificity determining region, is a large dynamic-binding surface. This appears to allow a high level of promiscuity in binding. Binding of a series of synthetic, phosphotyrosyl, peptidomimetic compounds designed to explore interactions in the pY + 3 pocket further demonstrates the ability of the SH2 domain to accommodate diverse ligands. The thermodynamic parameters of these interactions show dramatic enthalpy/entropy compensation. These data suggest that the v-Src SH2 domain does not have a highly specific secondary-binding site, which clearly presents a major hurdle to design selective inhibitors. Proteins 2008. (c) 2008 Wiley-Liss, Inc.

Structure, dynamics, and binding thermodynamics of the v-Src SH2 domain: Implications for drug design.,Taylor JD, Ababou A, Fawaz RR, Hobbs CJ, Williams MA, Ladbury JE Proteins. 2008 Jun 5;. PMID:18536014<ref>PMID:18536014</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2jyq" style="background-color:#fffaf0;"></div>

==See Also==
*[[Tyrosine kinase 3D structures|Tyrosine kinase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Rous sarcoma virus]]
[[Category: Ababou A]]
[[Category: Ladbury JE]]
[[Category: Taylor JD]]
[[Category: Williams MA]]