National Center for
2WZ0: L38v Sod1 Mutant Complexed With Aniline
Structural discovery of small molecule binding sites in Cu-Zn human superoxide dismutase familial amyotrophic lateral sclerosis mutants provides insights for lead optimization
J. Med. Chem. (2010) 53 p.1402-1406
Dominant inheritance of point mutations in CuZn superoxide dismutase (SOD1) is the best characterized subset of familial amyotrophic lateral sclerosis (FALS) and accounts for some 20% of the known familial cases. We report the discovery and visualization via cocrystallography of two ligand-binding pockets in human SOD1 and its pathogenic mutants that have opened up the real possibility of undertaking lead compound discovery using a fragment-based approach for therapeutic purposes for SOD1 associated motor neuron disease.