Strength of a bifurcated H bond

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 111; no. 11; pp. 4085 - 4090
• Main Authors: Feldblum, Esther S., Arkin, Isaiah T.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 18.03.2014; National Acad Sciences
• Subjects: Amides; Amino Acids - chemistry; Biological Sciences; Biophysics; Carbon Isotopes - chemistry; Dihedral angle; Hydrogen; Hydrogen Bonding; Hydrogen bonds; Hydroxyls; Lipid bilayers; Macromolecular Substances - chemistry; Models, Chemical; Molecular chemistry; Molecules; Oxygen Isotopes - chemistry; Proteins; Solvents; Spectroscopy, Fourier Transform Infrared; Vibrational frequencies; protein structure; FTIR; membrane proteins
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1319827111

Macromolecules are characterized by their particular arrangement of H bonds. Many of these interactions involve a single donor and acceptor pair, such as the regular H-bonding pattern between carbonyl oxygens and amide H+s four residues apart in α-helices. The H-bonding potential of some acceptors, however, leads to the phenomenon of overcoordination between two donors and one acceptor. Herein, using isotope-edited Fourier transform infrared measurements and density functional theory (DFT) calculations, we measured the strength of such bifurcated H bonds in a transmembrane α-helix. Frequency shifts of the 13C=18O amide I mode were used as a reporter of the strength of the bifurcated H bond from a thiol and hydroxyl H+ at residue i + 4. DFT calculations yielded very similar frequency shifts and an energy of -2.6 and -3.4 kcal/mol for the thiol and hydroxyl bifurcated H bonds, respectively. The strength of the intrahelical bifurcated H bond is consistent with its prevalence in hydrophobic environments and is shown to significantly impact side-chain rotamer distribution.