1m4c

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[[Image:1m4c.jpg|left|200px]]<br /><applet load="1m4c" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1m4c, resolution 2.40&Aring;" />
 
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'''Crystal Structure of Human Interleukin-2'''<br />
 
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==Overview==
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==Crystal Structure of Human Interleukin-2==
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Understanding binding properties at protein-protein interfaces has been, limited to structural and mutational analyses of natural binding partners, or small peptides identified by phage display. Here, we present a, high-resolution analysis of a nonpeptidyl small molecule, previously, discovered by medicinal chemistry [Tilley, J. W., et al. (1997) J. Am., Chem. Soc. 119, 7589-7590], which binds to the cytokine IL-2. The small, molecule binds to the same site that binds the IL-2 alpha receptor and, buries into a groove not seen in the free structure of IL-2. Comparison of, the bound and several free structures shows this site to be composed of, two subsites: one is rigid, and the other is highly adaptive., Thermodynamic data suggest the energy barriers between these conformations, are low. The subsites were dissected by using a site-directed screening, method called tethering, in which small fragments were captured by, disulfide interchange with cysteines introduced into IL-2 around these, subsites. X-ray structures with the tethered fragments show that the, subsite-binding interactions are similar to those observed with the, original small molecule. Moreover, the adaptive subsite tethered many more, compounds than did the rigid one. Thus, the adaptive nature of a, protein-protein interface provides sites for small molecules to bind and, underscores the challenge of applying structure-based design strategies, that cannot accurately predict a dynamic protein surface.
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<StructureSection load='1m4c' size='340' side='right'caption='[[1m4c]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1m4c]] 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=1M4C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1M4C FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1m4c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m4c OCA], [https://pdbe.org/1m4c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1m4c RCSB], [https://www.ebi.ac.uk/pdbsum/1m4c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1m4c ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[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.
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== Function ==
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[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.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/m4/1m4c_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1m4c ConSurf].
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<div style="clear:both"></div>
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==Disease==
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==See Also==
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Known disease associated with this structure: Severe combined immunodeficiency due to IL2 deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147680 147680]]
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*[[Interleukin 3D structures|Interleukin 3D structures]]
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__TOC__
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==About this Structure==
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</StructureSection>
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1M4C is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M4C OCA].
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==Reference==
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Binding of small molecules to an adaptive protein-protein interface., Arkin MR, Randal M, DeLano WL, Hyde J, Luong TN, Oslob JD, Raphael DR, Taylor L, Wang J, McDowell RS, Wells JA, Braisted AC, Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1603-8. Epub 2003 Feb 11. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12582206 12582206]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Arkin, M.A.]]
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[[Category: Arkin MA]]
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[[Category: Braisted, A.C.]]
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[[Category: Braisted AC]]
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[[Category: DeLano, W.L.]]
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[[Category: DeLano WL]]
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[[Category: Hyde, J.]]
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[[Category: Hyde J]]
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[[Category: Luong, T.N.]]
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[[Category: Luong TN]]
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[[Category: McDowell, R.S.]]
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[[Category: McDowell RS]]
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[[Category: Oslob, J.D.]]
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[[Category: Oslob JD]]
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[[Category: Randal, M.]]
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[[Category: Randal M]]
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[[Category: Raphael, D.R.]]
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[[Category: Raphael DR]]
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[[Category: Taylor, L.]]
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[[Category: Taylor L]]
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[[Category: Wang, J.]]
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[[Category: Wang J]]
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[[Category: Wells, J.A.]]
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[[Category: Wells JA]]
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[[Category: cytokine]]
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[[Category: four-helix bundle]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:21:51 2008''
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Current revision

Crystal Structure of Human Interleukin-2

PDB ID 1m4c

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