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

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

Author information

1
Institute of Biochemistry and Biotechnology, Martin-Luther-Universität Halle-Wittenberg, 06120 Halle, Germany.
2
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.

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.

PMID:
27336677
PMCID:
PMC5070668
DOI:
10.1039/c6ob00980h
[Indexed for MEDLINE]
Free PMC Article

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