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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.

SUBMITTER: Arnold U

PROVIDER: S-EPMC5070668 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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

Arnold Ulrich U Raines Ronald T RT

Organic & biomolecular chemistry 20160701 28

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 ...[more]

PMID: 27336677

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