Wide-angle X-ray solution scattering as a probe of ligand-induced conformational changes in proteins.
A chemical genetics approach to functional analysis of gene products utilizes high-throughput target-based screens of compound libraries to identify ligands that modulate the activity of proteins of interest. Candidates are further screened using functional assays designed specifically for the protein--and function--of interest, suffering from the need to customize the assay to each protein. An alternative strategy is to utilize a probe to detect the structural changes that usually accompany binding of a functional ligand. Wide-angle X-ray scattering from proteins provides a means to identify a broad range of ligand-induced changes in secondary, tertiary, and quaternary structure. The speed and accuracy of data acquisition, combined with the label-free targets and binding conditions achievable, indicate that WAXS is well suited as a moderate-throughput assay in the detection and analysis of protein-ligand interactions.
Biosciences Division, Argonne National Laboratory, 9700 South Cass Avenue, Argonne, Illinois 60439, USA.
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Fischetti
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Rodi
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Gore
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Makowski
D000426:Alcohol Dehydrogenase / Q000737:chemistry / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray / Q000379:methods; D008024:Ligands; D058619:Maltose-Binding Proteins; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D012542:Scattering, Radiation; D012996:Solutions; D014168:Transferrin / Q000737:chemistry / Q000378:metabolism; D014965:X-Rays
D002352:Carrier Proteins; D008024:Ligands; D058619:Maltose-Binding Proteins; D012996:Solutions; D014168:Transferrin; D000426:Alcohol Dehydrogenase