Recently, a connection between the genetic and environmental causes of Parkinson’s disease (PD) has been reported1-3. Among transition metals, manganese is an important metal that is both an essential and a toxic element at high doses. Cells have therefore to carefully control uptake and trafficking of this ion. It has been reported that a human PD gene, PARK9 and its homologue in yeast, YPK9, can prevent manganese-induced PD symptoms and protect neurons and cells from manganese poisoning. These genes encode a protein which, considering its richness in coordinating residues, looks like a metal transporter protein3, 4. We studied the possibility of metal binding to some portions of PARK9 and YPK9. In fact, from the inspection within the protein amino acid sequence, we detected very promising sites for metal interaction, excluding the membrane-spanning and the alpha-helical rich segments, probably not easily accessible to metals. They contain histidine and cysteine residues, known for being good metal anchoring sites, which are surrounded by residues bearing coordinating side chains, especially aspartate and glutamate, amino acids usually relevant in the homeostasis, transport or detoxification of manganese ions. Mono- and bi-dimensional NMR spectroscopy has been used to study the metal binding sites at different ligand to metal molar ratios and pH values. Among others, Mn(II) coordination with peptide involves imidazole Nδ or Nε of His and carboxyl γ-O of Asp and Glu residues. Six donor atoms participate in Mn(II) binding resulting in a distorted octahedral geometry, possibly involving bidentate interaction of carboxyl group. When cysteines are present in the sequence, Mn(II) coordination involves sulphur donor atoms from cysteine residues; additional oxygen donors from Glu or Asp complete the coordination sphere.

Metal interactions with peptide fragments from Parkinson’s disease genes / Maria Luisa Margherita, Ganadu; Maria, Antonietta Zoroddu; Serenella, Medici; Massimiliano Francesco, Peana; Giancarlo, Simula; Giuseppe, Puccio. - (2016). ((Intervento presentato al convegno 6th EuCheMS Chemistry Congress tenutosi a Siviglia, Spagna nel 11-15 settembre 2016.

Metal interactions with peptide fragments from Parkinson’s disease genes

GANADU, Maria Luisa Margherita;ZORODDU, Maria Antonietta;MEDICI, Serenella;PEANA, Massimiliano Francesco;
2016

Abstract

Recently, a connection between the genetic and environmental causes of Parkinson’s disease (PD) has been reported1-3. Among transition metals, manganese is an important metal that is both an essential and a toxic element at high doses. Cells have therefore to carefully control uptake and trafficking of this ion. It has been reported that a human PD gene, PARK9 and its homologue in yeast, YPK9, can prevent manganese-induced PD symptoms and protect neurons and cells from manganese poisoning. These genes encode a protein which, considering its richness in coordinating residues, looks like a metal transporter protein3, 4. We studied the possibility of metal binding to some portions of PARK9 and YPK9. In fact, from the inspection within the protein amino acid sequence, we detected very promising sites for metal interaction, excluding the membrane-spanning and the alpha-helical rich segments, probably not easily accessible to metals. They contain histidine and cysteine residues, known for being good metal anchoring sites, which are surrounded by residues bearing coordinating side chains, especially aspartate and glutamate, amino acids usually relevant in the homeostasis, transport or detoxification of manganese ions. Mono- and bi-dimensional NMR spectroscopy has been used to study the metal binding sites at different ligand to metal molar ratios and pH values. Among others, Mn(II) coordination with peptide involves imidazole Nδ or Nε of His and carboxyl γ-O of Asp and Glu residues. Six donor atoms participate in Mn(II) binding resulting in a distorted octahedral geometry, possibly involving bidentate interaction of carboxyl group. When cysteines are present in the sequence, Mn(II) coordination involves sulphur donor atoms from cysteine residues; additional oxygen donors from Glu or Asp complete the coordination sphere.
Metal interactions with peptide fragments from Parkinson’s disease genes / Maria Luisa Margherita, Ganadu; Maria, Antonietta Zoroddu; Serenella, Medici; Massimiliano Francesco, Peana; Giancarlo, Simula; Giuseppe, Puccio. - (2016). ((Intervento presentato al convegno 6th EuCheMS Chemistry Congress tenutosi a Siviglia, Spagna nel 11-15 settembre 2016.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11388/168712
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