A computational combinatorial approach identifies a protein inhibitor of superoxide dismutase 1 misfolding, aggregation, and cytotoxicity.

ABSTRACT: Molecular agents that specifically bind and neutralize misfolded and toxic superoxide dismutase 1 (SOD1) mutant proteins may find application in attenuating the disease progression of familial amyotrophic lateral sclerosis. However, high structural similarities between the wild-type and mutant SOD1 proteins limit the utility of this approach. Here we addressed this challenge by converting a promiscuous natural human IgG-binding domain, the hyperthermophilic variant of protein G (HTB1), into a highly specific aggregation inhibitor (designated HTB1_M) of two familial amyotrophic lateral sclerosis-linked SOD1 mutants, SOD1^G93A and SOD1^G85R We utilized a computational algorithm for mapping protein surfaces predisposed to HTB1 intermolecular interactions to const

SUBMITTER: Banerjee V 

PROVIDER: S-EPMC5612109 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature