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