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| - | [[Image:1m4c.jpg|left|200px]] | + | {{Seed}} |
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| | {{STRUCTURE_1m4c| PDB=1m4c | SCENE= }} | | {{STRUCTURE_1m4c| PDB=1m4c | SCENE= }} |
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| - | '''Crystal Structure of Human Interleukin-2'''
| + | ===Crystal Structure of Human Interleukin-2=== |
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| - | ==Overview==
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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.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_12582206}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 12582206 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_12582206}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Cytokine]] | | [[Category: Cytokine]] |
| | [[Category: Four-helix bundle]] | | [[Category: Four-helix bundle]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 00:36:51 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 2 23:10:50 2008'' |
Revision as of 20:10, 2 July 2008
Template:STRUCTURE 1m4c
Crystal Structure of Human Interleukin-2
Template:ABSTRACT PUBMED 12582206
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
Page seeded by OCA on Wed Jul 2 23:10:50 2008
Categories: Homo sapiens | Single protein | Arkin, M A. | Braisted, A C. | DeLano, W L. | Hyde, J. | Luong, T N. | McDowell, R S. | Oslob, J D. | Randal, M. | Raphael, D R. | Taylor, L. | Wang, J. | Wells, J A. | Cytokine | Four-helix bundle
