title: Further studies of the helix dipole model: effects of a free alpha-NH3+ or alpha-COO- group on helix stability.
abstract: Interactions between the alpha-helix peptide dipoles and charged groups close to the ends of the helix were found to be an important determinant of alpha-helix stability in a previous study. The charge on the N-terminal residue of the C-peptide from ribonuclease A was varied chiefly by changing the alpha-NH2 blocking group, and the correlation of helix stability with N-terminal charge was demonstrated. An alternative explanation for some of those results is that the succinyl and acetyl blocking groups stabilize the helix by hydrogen bonding to an unsatisfied main-chain NH group. The helix dipole model is tested here with peptides that contain either a free alpha-NH3+ or alpha-COO- group, and no other charged groups that would titrate with similar pKa's. This model predicts that alpha-NH3+ and alpha-COO- groups are helix-destabilizing and that the destabilizing interactions are electrostatic in origin. The hydrogen bonding model predicts that alpha-NH3+ and alpha-COO- groups are not themselves helix-destabilizing, but that an acetyl or amide blocking group at the N- or C-terminus, respectively, stabilizes the helix by hydrogen bonding to an unsatisfied main-chain NH or CO group. The results are as follows: (1) Removal of the charge from alpha-NH3+ and alpha-COO- groups by pH titration stabilizes an alpha-helix. (2) The increase in helix stability on pH titration of these groups is close to the increase produced by adding an acetyl or amide blocking group.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Biochemistry, Stanford University Medical Center, California 94305.
authors.forename: R
authors.initials: R
authors.lastname: Fairman
authors.forename: K R
authors.initials: KR
authors.lastname: Shoemaker
authors.forename: E J
authors.initials: EJ
authors.lastname: York
authors.forename: J M
authors.initials: JM
authors.lastname: Stewart
authors.forename: R L
authors.initials: RL
authors.lastname: Baldwin
mesh_terms: D000588:Amines / Q000032:analysis; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004594:Electrophysiology; D006863:Hydrogen-Ion Concentration; D010455:Peptides / Q000032:analysis*; D011487:Protein Conformation; D013386:Succinates / Q000032:analysis
chemical_list: D000588:Amines; D010455:Peptides; D013386:Succinates