title: Replacing a single atom accelerates the folding of a protein and increases its thermostability.
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.
authors.affiliation: Institute of Biochemistry and Biotechnology, Martin-Luther-Universität Halle-Wittenberg, 06120 Halle, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Arnold
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA. rtraines@wisc.edu and Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
authors.forename: Ronald T
authors.initials: RT
authors.lastname: Raines
mesh_terms: D019943:Amino Acid Substitution; D054879:Halogenation; D008958:Models, Molecular; D011392:Proline / Q000031:analogs & derivatives* / Q000235:genetics; D011487:Protein Conformation; D017510:Protein Folding; D055550:Protein Stability; D012259:Ribonuclease, Pancreatic / Q000737:chemistry* / Q000235:genetics; D013696:Temperature; D013816:Thermodynamics
chemical_list: D011392:Proline; D012259:Ribonuclease, Pancreatic