ESI-MS and tandem mass spectrometry have demonstrated their potential for characterizing noncovalent protein-ligand complexes, including protein-metal complexes. Studies have shown ESI-MS to be a useful tool for identifying metal ion speciation and for measuring metal binding stoichiometry. However, determining the sites of ligand binding on protein targets by mass spectrometry has been difficult. We have used a combination of ESI-MS/MS, FT-ICR, and ECD to probe the binding of small molecule ligands to Parkinson's disease related alpha-synuclein protein and other proteins [1]. The ligand binding sites are elucidated directly by top-down ESI-MS/MS experiments. Parkinson's disease (PD) is the second most common neurodegenerative disorder. Patients with PD suffer from tremors, muscle rigidity, slowness in movement and sometimes postural instability. These symptoms all involve the loss of dopamine, a neurotransmitter. In the brain, dopamine is mainly generated in dopaminergic neurons cell at the substantia nigra area. Accumulation of Lewy bodies in dopaminergic neurons causes progressive loss of nerve cells and dopamine, and therefore, loss of control of muscle.
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