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Protein prosthesis: ?-peptides as reverse-turn surrogates.

ABSTRACT: The introduction of non-natural modules could provide unprecedented control over folding/unfolding behavior, conformational stability, and biological function of proteins. Success requires the interrogation of candidate modules in natural contexts. Here, expressed protein ligation is used to replace a reverse turn in bovine pancreatic ribonuclease (RNase A) with a synthetic ?-dipeptide: ?²-homoalanine-?³-homoalanine. This segment is known to adopt an unnatural reverse-turn conformation that contains a 10-membered ring hydrogen bond, but one with a donor-acceptor pattern opposite to that in the 10-membered rings of natural reverse turns. The RNase A variant has intact enzymatic activity, but unfolds more quickly and has diminished conformational stability relative to native RNase A. These data indicate that hydrogen-bonding pattern merits careful consideration in the selection of beneficial reverse-turn surrogates.

SUBMITTER: Arnold U

PROVIDER: S-EPMC3595457 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Protein prosthesis: β-peptides as reverse-turn surrogates.

Arnold Ulrich U Huck Bayard R BR Gellman Samuel H SH Raines Ronald T RT

Protein science : a publication of the Protein Society 20130117 3

The introduction of non-natural modules could provide unprecedented control over folding/unfolding behavior, conformational stability, and biological function of proteins. Success requires the interrogation of candidate modules in natural contexts. Here, expressed protein ligation is used to replace a reverse turn in bovine pancreatic ribonuclease (RNase A) with a synthetic β-dipeptide: β²-homoalanine-β³-homoalanine. This segment is known to adopt an unnatural reverse-turn conformation that cont ...[more]

PMID: 23238807

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