Anticooperativity in a Glu-Lys-Glu salt bridge triplet in an isolated alpha-helical peptide

Biochemistry. 2005 Aug 9;44(31):10449-56. doi: 10.1021/bi0508690.

Abstract

Salt bridges between oppositely charged side chains are well-known to stabilize protein structure, though their contributions vary considerably. Here we study Glu-Lys and Lys-Glu salt bridges, formed when the residues are spaced i, i + 4 surface of an isolated alpha-helix in aqueous solution. Both are stabilizing by -0.60 and -1.02 kcal/mol, respectively, when the interacting residues are fully charged. When the side chains are spaced i, i + 4, i + 8, forming a Glu-Lys-Glu triplet, the second salt bridge provides no additional stabilization to the helix. We attribute this to the inability of the central Lys to form two salt bridges simultaneously. Analysis of these salt bridges in protein structures shows that the Lys-Glu interaction is dominant, with the side chains of the Glu-Lys pair far apart.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Circular Dichroism
  • Hydrogen-Ion Concentration
  • Molecular Sequence Data
  • Oligopeptides / chemical synthesis*
  • Oligopeptides / isolation & purification*
  • Potentiometry
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Salts*
  • Solvents
  • Thermodynamics

Substances

  • Oligopeptides
  • Salts
  • Solvents