Ligand Binding and Aggregation of Pathogenic Sod1.

摘要: Mutations in the gene encoding Cu/Zn superoxide dismutase-1 cause amyotrophic lateral sclerosis. Superoxide mutations decrease protein stability and promote aggregation. The mutant monomer is thought to be an intermediate pathway from dimer aggregate. Here we find that monomeric copper-apo, zinc-holo structurally perturbed apo-protein aggregates without reattainment of monomer-dimer equilibrium. Intervention stabilize inhibit aggregation regarded as a potential therapeutic strategy. We describe protein-ligand interactions for two compounds, Isoproterenol 5-fluorouridine, highlighted stabilizers. both compounds interact with at key region identified core fibrillar aggregates, β-barrel loop II-strand 3, rather than proposed interface site. This illustrates need direct structural observations when developing protein-targeted therapeutics.