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

July 28, 2017

Title

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

Author

Ulrich Arnold, Ronald T. Raines

Year

2016

Journal

Organic and Biomolecular Chemistry

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 4Shydrogen of a proline residue with fluorine is known to elicit stereoelectronic effects that favor acis 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.

Instrument

J-815

Keywords

Circular dichroism, Secondary structure, Tertiary structure, Thermal stability, Protein denaturation, Protein folding, Thermodynamics, Biochemistry