A designed beta-hairpin peptide for molecular recognition of ATP in water.
A designed 12-residue beta-hairpin peptide with a diagonal tryptophan (Trp) pair was shown to bind ATP in water through a combination of aromatic and electrostatic interactions. The affinity for ATP was 5800 M-1 (DeltaG approximately -5.0 kcal/mol), a remarkable affinity for a short, structured peptide in water, consisting of entirely natural amino acid residues. Proton NMR measurements indicate that the adenine ring of the nucleotide is intercalated between the diagonal tryptophans in the bound state. Delineation of the contributions to ATP binding to the hairpin suggest that aromatic interactions contribute approximately -1.8 kcal/mol, while individual electrostatic interactions involving the ATP phosphates and positively charged side chains of the hairpin contribute approximately -1 kcal/mol each. The designed beta-hairpin receptor presents a novel minimalist system to investigate the energetic contributions to protein-nucleic acid recognition through the surface of a beta-sheet.
Butterfield
Sara M
SM
Department of Chemistry, University of North Carolina at Chapel Hill, CB 3290, Chapel Hill, North Carolina 27599, USA.
Waters
Marcey L
ML
D000255:Adenosine Triphosphate / Q000737:chemistry*; D000595:Amino Acid Sequence; D007700:Kinetics; D009842:Oligopeptides / Q000737:chemistry*; D011487:Protein Conformation; D013816:Thermodynamics; D014867:Water / Q000737:chemistry*
D009842:Oligopeptides; D014867:Water; D000255:Adenosine Triphosphate