Replacing a single atom accelerates the folding of a protein and increases its thermostability

Org Biomol Chem. 2016 Jul 12;14(28):6780-5. doi: 10.1039/c6ob00980h.

Abstract

The conformational attributes of proline can have a substantial effect on the folding of polypeptide chains into a native structure and on the stability of that structure. Replacing the 4S hydrogen of a proline residue with fluorine is known to elicit stereoelectronic effects that favor a cis peptide bond. Here, semisynthesis is used to replace a cis-proline residue in ribonuclease A with (2S,4S)-4-fluoroproline. This subtle substitution accelerates the folding of the polypeptide chain into its three-dimensional structure and increases the thermostability of that structure without compromising its catalytic activity. Thus, an appropriately situated fluorine can serve as a prosthetic atom in the context of a protein.

MeSH terms

  • Amino Acid Substitution
  • Halogenation
  • Models, Molecular
  • Proline / analogs & derivatives*
  • Proline / genetics
  • Protein Conformation
  • Protein Folding*
  • Protein Stability
  • Ribonuclease, Pancreatic / chemistry*
  • Ribonuclease, Pancreatic / genetics
  • Temperature
  • Thermodynamics

Substances

  • Proline
  • Ribonuclease, Pancreatic