1NBP

Crystal Structure Of Human Interleukin-2 Y31C Covalently Modified At C31 With 3-Mercapto-1-(1,3,4,9-tetrahydro-B-carbolin-2-yl)-propan-1-one

Summary for 1NBP

• Entry DOI: 10.2210/pdb1nbp/pdb
• Related: 1M47 1M48 1M49 1M4A 1M4B 1M4C
• Descriptor: Interleukin-2, SULFATE ION, 3-MERCAPTO-1-(1,3,4,9-TETRAHYDRO-B-CARBOLIN-2-YL)-PROPAN-1-ONE, ... (4 entities in total)
• Functional Keywords: cytokine, four-helix bundle, small molecule complex
• Biological source: Homo sapiens (human)
• Cellular location: Secreted: P60568
• Total number of polymer chains: 1
• Total formula weight: 15732.37

Authors

Hyde, J.,Braisted, A.C.,Randal, M.,Arkin, M.R. (deposition date: 2002-12-03, release date: 2002-12-18, Last modification date: 2024-10-30)

Primary citation

Hyde, J.,Braisted, A.C.,Randal, M.,Arkin, M.R.
Discovery and characterization of cooperative ligand binding in the adaptive region of interleukin-2
Biochemistry, 42:6475-6483, 2003

PubMed 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.

PubMed: 12767230
DOI: 10.1021/bi034138g

Experimental method

X-RAY DIFFRACTION (2.2 Å)