1m4c

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[[Image:1m4c.jpg|left|200px]]
 
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{{Structure
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==Crystal Structure of Human Interleukin-2==
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|PDB= 1m4c |SIZE=350|CAPTION= <scene name='initialview01'>1m4c</scene>, resolution 2.40&Aring;
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<StructureSection load='1m4c' size='340' side='right'caption='[[1m4c]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND=
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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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|ACTIVITY=
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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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|GENE=
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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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|DOMAIN=
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</table>
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|RELATEDENTRY=[[1m47|1M47]], [[1m48|1M48]], [[1m49|1M49]], [[1m4a|1M4A]], [[1m4b|1M4B]]
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== Disease ==
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1m4c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m4c OCA], [http://www.ebi.ac.uk/pdbsum/1m4c PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1m4c RCSB]</span>
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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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}}
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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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'''Crystal Structure of Human Interleukin-2'''
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==See Also==
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*[[Interleukin 3D structures|Interleukin 3D structures]]
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__TOC__
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==Overview==
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</StructureSection>
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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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==About this Structure==
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1M4C is a [[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://www.ncbi.nlm.nih.gov/pubmed/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 Sun Mar 30 22:11:03 2008''
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Current revision

Crystal Structure of Human Interleukin-2

PDB ID 1m4c

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