A Designed β-Hairpin Peptide for Molecular Recognition of ATP in Water

• Published in: Journal of the American Chemical Society 2003-08, Vol.125 (32), p.9580-9581
• Main Authors: Butterfield, Sara M, Waters, Marcey L
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate - chemistry; Amino Acid Sequence; Biological and medical sciences; Chemistry; Exact sciences and technology; Fundamental and applied biological sciences. Psychology; General and physical chemistry; In solution. Condensed state. Thin layers; Kinetics; Molecular biophysics; Oligopeptides - chemistry; Physico-chemical properties of biomolecules; Protein Conformation; Solution properties; Solutions; Thermodynamics; Water - chemistry
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja0359254

A designed 12-residue β-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 (ΔG ≈ −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 β-hairpin receptor presents a novel minimalist system to investigate the energetic contributions to protein−nucleic acid recognition through the surface of a β-sheet.