title: Acceleration of the folding of acylphosphatase by stabilization of local secondary structure.
abstract: The addition of trifluoroethanol or hexafluoroisopropanol converts the apparent two-state folding of acylphosphatase, a small alpha/beta protein, into a multistate mechanism where secondary structure accumulates significantly in the denatured state before folding to the native state. This results in a marked acceleration of folding as revealed by following the intrinsic fluorescence and circular dichroism changes upon folding. The folding rate is at a maximum when the secondary-structure content of the denatured state corresponds to that of the native state, while further stabilization of secondary structure decreases the folding rate. These findings indicate that stabilization of intermediate structure can either enhance or retard folding depending on its nature and content of native-like interactions.
authors: Oxford Centre for Molecular Sciences, New Chemistry Laboratory, University of Oxford, UK.
authors: F
authors: F
authors: Chiti
authors: N
authors: N
authors: Taddei
authors: P
authors: P
authors: Webster
authors: D
authors: D
authors: Hamada
authors: T
authors: T
authors: Fiaschi
authors: G
authors: G
authors: Ramponi
authors: C M
authors: CM
authors: Dobson
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000737:chemistry* / Q000187:drug effects; D006801:Humans; D006860:Hydrogen Bonding; D008956:Models, Chemical; D008958:Models, Molecular; D018482:Muscle, Skeletal / Q000201:enzymology; D020005:Propanols / Q000737:chemistry / Q000494:pharmacology; D011487:Protein Conformation; D011489:Protein Denaturation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D014270:Trifluoroethanol / Q000737:chemistry / Q000494:pharmacology; D000097024:Acylphosphatase; D006845:Hydrocarbons, Fluorinated
chemical_list: D017766:Acid Anhydride Hydrolases; D020005:Propanols; D014270:Trifluoroethanol; D000097024:Acylphosphatase; C001337:hexafluoroisopropanol; D006845:Hydrocarbons, Fluorinated