Abstract：
:The cytokine hormone interleukin-2 (IL-2) contains a highly adaptive region that binds small, druglike molecules. The binding properties of this adaptive region have been explored using a "tethering" method that relies on the formation of a disulfide bond between the protein and small-molecule ligands. Using tethering, surface plasmon resonance (SPR), and X-ray crystallography, we have discovered that the IL-2 adaptive region contains at least two cooperative binding sites where the binding of a first ligand to one site promotes or antagonizes the binding of a second ligand to the second site. Cooperative energies of interaction of -2 kcal/mol are observed. The observation that the adaptive region contains two adjacent sites may lead to the development of tight-binding antagonists of a protein-protein interaction. Cooperative ligand binding in the adaptive region of IL-2 underscores the importance of protein dynamics in molecular recognition. The tethering approach provides a novel and general strategy for discovering such cooperative binding interactions in specific, flexible regions of protein structure.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Hyde J,Braisted AC,Randal M,Arkin MRdoi
10.1021/bi034138gsubject
Has Abstractpub_date
2003-06-03 00:00:00pages
6475-83issue
21eissn
0006-2960issn
1520-4995journal_volume
42pub_type
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