
doi: 10.1021/ja0392519
pmid: 15264834
Specific protein-ligand interactions are central to biological control. Although structure determination provides important insight into these interactions, it does not address dynamic events that occur during binding. While many biophysical techniques can provide a global view of these dynamics, NMR can be used to derive site-specific dynamics at atomic resolution. Here we show how NMR line shapes can be analyzed to identify long-lived kinetic intermediates for individual amino acids on the reaction pathway for a protein-ligand interaction. Different ligands cause different intermediate states. The lifetimes of these states determine the specificity of binding. This novel approach provides a direct, site-specific visualization of the kinetic mechanism of protein-ligand interactions.
Models, Molecular, Antigens, Polyomavirus Transforming, Titrimetry, Ligands, Protein Structure, Tertiary, src Homology Domains, Kinetics, Phosphatidylinositol 3-Kinases, src-Family Kinases, Receptors, Platelet-Derived Growth Factor, Phosphotyrosine, Nuclear Magnetic Resonance, Biomolecular
Models, Molecular, Antigens, Polyomavirus Transforming, Titrimetry, Ligands, Protein Structure, Tertiary, src Homology Domains, Kinetics, Phosphatidylinositol 3-Kinases, src-Family Kinases, Receptors, Platelet-Derived Growth Factor, Phosphotyrosine, Nuclear Magnetic Resonance, Biomolecular
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