title: Correlation between protein function and ligand binding profiles.
abstract: We report that proteins with the same function bind the same set of small molecules from a standardized chemical library. This observation led to a quantifiable and rapidly adaptable method for protein functional analysis using experimentally derived ligand binding profiles. Ligand binding is measured using a high-throughput NMR ligand affinity screen with a structurally diverse chemical library. The method was demonstrated using a set of 19 proteins with a range of functions. A statistically significant similarity in ligand binding profiles was only observed between the two functionally identical albumins and between the five functionally similar amylases. This new approach is independent of sequence, structure, or evolutionary information and, therefore, extends our ability to analyze and functionally annotate novel genes.
authors.affiliation: Department of Chemistry, University of Nebraska-Lincoln, Lincoln, Nebraska 68588-0304, United States.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Shortridge
authors.forename: Michael
authors.initials: M
authors.lastname: Bokemper
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Copeland
authors.forename: Jaime L
authors.initials: JL
authors.lastname: Stark
authors.forename: Robert
authors.initials: R
authors.lastname: Powers
mesh_terms: D000681:Amylases / Q000378:metabolism; D006801:Humans; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D058977:Molecular Sequence Annotation / Q000379:methods*; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism* / Q000502:physiology*; D040901:Proteomics / Q000379:methods*; D012709:Serum Albumin / Q000378:metabolism
chemical_list: D008024:Ligands; D011506:Proteins; D012709:Serum Albumin; D000681:Amylases