1m4c
From Proteopedia
(New page: 200px<br /> <applet load="1m4c" size="450" color="white" frame="true" align="right" spinBox="true" caption="1m4c, resolution 2.40Å" /> '''Crystal Structure o...) |
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caption="1m4c, resolution 2.40Å" /> | caption="1m4c, resolution 2.40Å" /> | ||
'''Crystal Structure of Human Interleukin-2'''<br /> | '''Crystal Structure of Human Interleukin-2'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 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:// | + | 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]. |
==Reference== | ==Reference== | ||
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[[Category: four-helix bundle]] | [[Category: four-helix bundle]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:21:51 2008'' |
Revision as of 14:21, 15 February 2008
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Crystal Structure of Human Interleukin-2
Contents |
Overview
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.
Disease
Known disease associated with this structure: Severe combined immunodeficiency due to IL2 deficiency OMIM:[147680]
About this Structure
1M4C is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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:12582206
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