title: 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.
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Shlomi
authors.initials: S
authors.lastname: Dagan
authors.forename: Tzachi
authors.initials: T
authors.lastname: Hagai
authors.forename: Yulian
authors.initials: Y
authors.lastname: Gavrilov
authors.forename: Ruti
authors.initials: R
authors.lastname: Kapon
authors.forename: Yaakov
authors.initials: Y
authors.lastname: Levy
authors.forename: Ziv
authors.initials: Z
authors.lastname: Reich
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000737:chemistry* / Q000235:genetics; D055592:Biophysical Phenomena; D003198:Computer Simulation; D019277:Entropy; D004795:Enzyme Stability; D006801:Humans; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D016254:Mutagenesis, Insertional; D016297:Mutagenesis, Site-Directed; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics; D017510:Protein Folding; D055550:Protein Stability; D013816:Thermodynamics; D000097024:Acylphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D050505:Mutant Proteins; D000097024:Acylphosphatase
keywords: loop closure entropy; molecular dynamics; protein folding