title: Simplicity within the complexity: bilateral impact of DMSO on the functional and unfolding patterns of α-chymotrypsin.
abstract: New understanding of the fundamental links between protein stability, conformational flexibility and function, can be gained through synergic studies on their catalytic and folding/unfolding properties under the influence of stabilizing/destabilizing additives. We explored an impact of dimethyl sulfoxide (DMSO), the moderate effector of multilateral action, on the kinetic (functional) and thermodynamic (thermal unfolding) patterns of a hydrolytic enzyme, α-chymotrypsin (α-CT), over a wide range of additive concentrations, 0-70% (v/v). Both the calorimetric and kinetic data exhibited rich behavior pointing to the complex interplay of global/local stability (and flexibility) patterns. The complex action of DMSO is explained through the negative and positive preferential solvation motifs that prevail for the extreme opposite, native-like and unfolded states, respectively, implying essential stabilization of compact domains by enhancement of interfacial water networks and destabilization of a flexible active site by direct binding of DMSO to the unoccupied specific positions intended for elongated polypeptide substrates.
authors.affiliation: Institute for Biophysics and Bionanosciences at the Department of Physics, I. Javakhishvili Tbilisi State University, I. Chavchavadze Ave. 3, 0128 Tbilisi, Georgia.
authors.forename: Tatyana
authors.initials: T
authors.lastname: Tretyakova
authors.forename: Mikhael
authors.initials: M
authors.lastname: Shushanyan
authors.forename: Tamar
authors.initials: T
authors.lastname: Partskhaladze
authors.forename: Maya
authors.initials: M
authors.lastname: Makharadze
authors.forename: Rudi
authors.initials: R
authors.lastname: van Eldik
authors.forename: Dimitri E
authors.initials: DE
authors.lastname: Khoshtariya
mesh_terms: D002151:Calorimetry; D020134:Catalytic Domain; D002918:Chymotrypsin / Q000737:chemistry / Q000378:metabolism*; D004121:Dimethyl Sulfoxide / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D055550:Protein Stability; D058767:Protein Unfolding; D013816:Thermodynamics
chemical_list: D002918:Chymotrypsin; C117608:alpha-chymotrypsin; D004121:Dimethyl Sulfoxide