Probing the free energy landscapes of ALS disease mutants of SOD1 by NMR spectroscopy.

ABSTRACT: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that, in some cases, has been linked with mutations to the antioxidant metalloenzyme superoxide dismutase (SOD1). Although the mature form of this enzyme is highly stable and resistant to aggregation, the most immature form, lacking metal and a stabilizing intrasubunit disulfide bond, apoSOD1^2SH, is dynamic and hypothesized to be a major cause of toxicity in vivo. Previous solution NMR studies of wild-type apoSOD1^2SH have shown that the ground state interconverts with a series of sparsely populated and transiently formed conformers, some of which have aberrant nonnative structures. Here, we study seven disease mutants of apoSOD1^2SH and characterize their free energy landscapes as a first ste

SUBMITTER: Sekhar A 

PROVIDER: S-EPMC5111666 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature