This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
1m49
From Proteopedia
| Line 1: | Line 1: | ||
[[Image:1m49.gif|left|200px]] | [[Image:1m49.gif|left|200px]] | ||
| - | + | <!-- | |
| - | + | The line below this paragraph, containing "STRUCTURE_1m49", creates the "Structure Box" on the page. | |
| - | + | You may change the PDB parameter (which sets the PDB file loaded into the applet) | |
| - | + | or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |
| - | | | + | or leave the SCENE parameter empty for the default display. |
| - | | | + | --> |
| - | + | {{STRUCTURE_1m49| PDB=1m49 | SCENE= }} | |
| - | + | ||
| - | + | ||
| - | }} | + | |
'''Crystal Structure of Human Interleukin-2 Complexed with SP-1985''' | '''Crystal Structure of Human Interleukin-2 Complexed with SP-1985''' | ||
| Line 37: | Line 34: | ||
[[Category: Wang, J.]] | [[Category: Wang, J.]] | ||
[[Category: Wells, J A.]] | [[Category: Wells, J A.]] | ||
| - | [[Category: | + | [[Category: Cytokine]] |
| - | [[Category: | + | [[Category: Four-helix bundle]] |
| - | [[Category: | + | [[Category: Small molecule complex]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 00:36:38 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 21:36, 2 May 2008
Crystal Structure of Human Interleukin-2 Complexed with SP-1985
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.
About this Structure
1M49 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 Sat May 3 00:36:38 2008
