Enthalpic barriers dominate the folding and unfolding of the human Cu, Zn superoxide dismutase monomer.

ABSTRACT: The rate-limiting step in the formation of the native dimeric state of human Cu, Zn superoxide dismutase (SOD1) is a very slow monomer folding reaction that governs the lifetime of its unfolded state. Mutations at dozens of sites in SOD1 are known to cause a fatal motor neuron disease, amyotrophic lateral sclerosis, and recent experiments implicate the unfolded state as a source of soluble oligomers and histologically observable aggregates thought to be responsible for toxicity. To determine the thermodynamic properties of the transition state ensemble (TSE) limiting the folding of this high-contact-order β-sandwich motif, we performed a combined thermal/urea denaturation thermodynamic/kinetic analysis. The barriers to folding and unfolding are dominated by the activation enthalpy at 298 K

SUBMITTER: Kayatekin C 

PROVIDER: S-EPMC3712906 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature