Evolutionary Analyses of Sequence and Structure Space Unravel the Structural Facets of SOD1.

ABSTRACT: Superoxide dismutase (SOD) is the primary enzyme of the cellular antioxidant defense cascade. Misfolding, concomitant oligomerization, and higher order aggregation of human cytosolic SOD are linked to amyotrophic lateral sclerosis (ALS). Although, with two metal ion cofactors SOD1 is extremely robust, the de-metallated apo form is intrinsically disordered. Since the rise of oxygen-based metabolism and antioxidant defense systems are evolutionary coupled, SOD is an interesting protein with a deep evolutionary history. We deployed statistical analysis of sequence space to decode evolutionarily co-varying residues in this protein. These were validated by applying graph theoretical modelling to understand the impact of the presence of metal ion co-factors in dictating the disordered (apo) to h

SUBMITTER: Chowdhury S 

PROVIDER: S-EPMC6995586 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature