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Modulating the Folding Landscape of Superoxide Dismutase 1 with Targeted Molecular Binders
Author(s) -
Bunck David N.,
Atsavapranee Beatriz,
Museth Anna K.,
VanderVelde David,
Heath James R.
Publication year - 2018
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201802269
Subject(s) - sod1 , amyotrophic lateral sclerosis , superoxide dismutase , folding (dsp implementation) , epitope , protein folding , chemistry , peptide , energy landscape , biochemistry , microbiology and biotechnology , biophysics , disease , computational biology , biology , oxidative stress , medicine , antigen , immunology , pathology , electrical engineering , engineering
Amyotrophic lateral sclerosis, or Lou Gehrig's disease, is characterized by motor neuron death, with average survival times of two to five years. One cause of this disease is the misfolding of superoxide dismutase 1 (SOD1), a phenomenon influenced by point mutations spanning the protein. Herein, we used an epitope‐specific high‐throughput screen to identify a peptide ligand that stabilizes the SOD1 native conformation and accelerates its folding by a factor of 2.5. This strategy may be useful for fundamental studies of protein energy landscapes as well as designing new classes of therapeutics.