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Stabilization of a protein conferred by an increase in folded state entropy.

ABSTRACT: Entropic stabilization of native protein structures typically relies on strategies that serve to decrease the entropy of the unfolded state. Here we report, using a combination of experimental and computational approaches, on enhanced thermodynamic stability conferred by an increase in the configurational entropy of the folded state. The enhanced stability is observed upon modifications of a loop region in the enzyme acylphosphatase and is achieved despite significant enthalpy losses. The modifications that lead to increased stability, as well as those that result in destabilization, however, strongly compromise enzymatic activity, rationalizing the preservation of the native loop structure even though it does not provide the protein with maximal stability or kinetic foldability.

SUBMITTER: Dagan S

PROVIDER: S-EPMC3696814 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Stabilization of a protein conferred by an increase in folded state entropy.

Dagan Shlomi S Hagai Tzachi T Gavrilov Yulian Y Kapon Ruti R Levy Yaakov Y Reich Ziv Z

Proceedings of the National Academy of Sciences of the United States of America 20130610 26

Entropic stabilization of native protein structures typically relies on strategies that serve to decrease the entropy of the unfolded state. Here we report, using a combination of experimental and computational approaches, on enhanced thermodynamic stability conferred by an increase in the configurational entropy of the folded state. The enhanced stability is observed upon modifications of a loop region in the enzyme acylphosphatase and is achieved despite significant enthalpy losses. The modifi ...[more]

PMID: 23754389

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