View source for 1qvn


==Structure of SP4160 Bound to IL-2 V69A==
<StructureSection load='1qvn' size='340' side='right'caption='[[1qvn]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1qvn]] 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=1QVN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1QVN 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]] 2.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FRI:2-GUANIDINO-4-METHYL-PENTANOIC+ACID+[2-(4-{5-[4-(4-ACETYLAMINO-BENZYLOXY)-2,3-DICHLORO-PHENYL]-2-METHYL-2H-PYRAZOL-3-YL}-PIPERIDIN-1-YL)-2-OXO-ETHYL]-AMIDE'>FRI</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=1qvn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qvn OCA], [https://pdbe.org/1qvn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1qvn RCSB], [https://www.ebi.ac.uk/pdbsum/1qvn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1qvn ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/IL2_HUMAN IL2_HUMAN] Note=A chromosomal aberration involving IL2 is found in a form of T-cell acute lymphoblastic leukemia (T-ALL). Translocation t(4;16)(q26;p13) with involves TNFRSF17.
== Function ==
[https://www.uniprot.org/uniprot/IL2_HUMAN IL2_HUMAN] Produced by T-cells in response to antigenic or mitogenic stimulation, this protein is required for T-cell proliferation and other activities crucial to regulation of the immune response. Can stimulate B-cells, monocytes, lymphokine-activated killer cells, natural killer cells, and glioma cells.
== 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/qv/1qvn_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=1qvn ConSurf].
<div style="clear:both"></div>
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== Publication Abstract from PubMed ==
Protein-protein complexes remain enticing, but extremely challenging, targets for small-molecule drug discovery. In a rare example described earlier, a high-affinity small molecule, SP4206 (Kd approximately 70 nM), was found to block binding of the IL-2alpha receptor (IL-2Ralpha) to IL-2 (Kd approximately 10 nM). Recently, the structure of the IL-2/IL-2Ralpha complex was solved [Rickert, M., Wang, X., Boulanger, M. J., Goriatcheva, N., Garcia, K. C. (2005) Science 308:1477-1480]. Using structural and functional analysis, we compare how SP4206 mimics the 83-fold larger IL-2Ralpha in binding IL-2. The binding free energy per contact atom (ligand efficiency) for SP4206 is about twice that of the receptor because of a smaller, but overlapping, contact epitope that insinuates into grooves and cavities not accessed by the receptor. Despite its independent design, the small molecule has a similar, but more localized, charge distribution compared with IL-2Ralpha. Mutational studies show that SP4206 targets virtually the same critical "hot-spot" residues on IL-2 that drive binding of IL-2Ralpha. Moreover, a mutation that enhances binding to the IL-2Ralpha near these hot spots also enhances binding to SP4206. Although the protein and small molecule do bind the same hot spot, they trap very different conformations of IL-2 because of its flexible nature. Our studies suggest that precise structural mimics of receptors are not required for high-affinity binding of small molecules, and they show that there are multiple solutions to tight binding at shared and adaptive hot spots.

Hot-spot mimicry of a cytokine receptor by a small molecule.,Thanos CD, DeLano WL, Wells JA Proc Natl Acad Sci U S A. 2006 Oct 17;103(42):15422-7. Epub 2006 Oct 10. PMID:17032757<ref>PMID:17032757</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 1qvn" style="background-color:#fffaf0;"></div>

==See Also==
*[[Interleukin 3D structures|Interleukin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Delano WL]]
[[Category: Thanos CD]]
[[Category: Wells JA]]