Studies on the the conformation and aggregation of SOD1 and the screening of its inhibitors by ion m

• 作 者: Xiaoyu Zhuang Shu Liu Zhiqiang Liu Fengrui Song
• 机 构: National Center of Mass Spectrometry in Changchun,Changchun Institute of Applied Chemistry,Chinese A
• 出 处: 第34届(2016)中国质谱学会学术年会
• 发表日期: 2016年3期
• 关键词: Superoxide dismutase Spatial structure Non-covalent interactions Native mass spe

　　The misfolding and aggregation of proteins are closely related to many neurodegenerative conformational diseases.Among these diseases,the misfolding and aggregation of metal-deficient and oxidation-induced Cu,Zn superoxide dismutase(SOD1)plays important roles in the onset and development of amyotrophic lateral sclerosis(ALS).Since the spatial structure of this metalloenzyme is closely related to its bioactivities,in this study we investigate the structural and conformational changes of SOD1in the gas phase by electrospray ionization mass spectrometry(ESI-MS)and ionmobility(IM)separation combined with tandem mass spectrometry(MS/MS).Three different dimeric and two monomeric conformers were observed; three unfolding and dissociation pathways were also identified.In order to screen the inhibitors of dissociation and aggregation of SOD1,native mass spectrometry coupled with ion mobility separation was used to study the non-covalent interactions between SOD1 and flavonoid compounds.ESI-MS was used to detect the SOD1-flavonoid complexes and determine their binding strengths.The complement of ion mobility separation allowed comparison in the binding affinities between flavonoid isomers,and investigated the effects of flavonoids on the conformation and the dissociation of SOD1 dimer.Moreover,fluorescence spectrometry and molecular docking were performed to gain insight into the free energies of SOD1-flavonoid complexes.This analytical strategy could be applied to study the interactions between SOD1 and other drug-like molecules that may have the effect to reduce the aggregation.