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首页> 外文期刊>Dalton transactions: An international journal of inorganic chemistry >Mn(ii) and Zn(ii) interactions with peptide fragments from Parkinson's disease genes
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Mn(ii) and Zn(ii) interactions with peptide fragments from Parkinson's disease genes

机译:Mn(ii)和Zn(ii)与帕金森氏病基因的肽片段相互作用

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Two peptide sequences from PARK9 Parkinson's disease gene, ProAspGluLysHisGluLeu, (P _1D _2E _3K _4H _5E _6L _7) (1) and PheCysGlyAspGlyAlaAsnAspCysGly (F _1C _2G _3D _4G _5A _6N _7D _8C _9G _(10)) (2) were tested for Mn(ii), Zn(ii) and Ca(ii) binding. The fragments are located from residues 1165 to 1171 and 1184 to 1193 in the PARK9 encoded protein. This protein can protect cells from poisoning of manganese, which is an environmental risk factor for a Parkinson's disease-like syndrome. Mono- and bi-dimensional NMR spectroscopy has been used to understand the details of metal binding sites at different pH values and at different ligand to metal molar ratios. Mn(ii) and Zn(ii) coordination with peptide (1) involves imidazole N _ε or N _δ of His _5 and carboxyl γ-O of Asp _2, Glu _3 and Glu _6 residues. Six donor atoms participate in Mn(ii) binding resulting in a distorted octahedral geometry, possibly involving bidentate interaction of carboxyl groups; four donor atoms participate in Zn(ii) binding resulting in a tetracoordinate geometry. Mn(ii) and Zn(ii) coordination involves the two cysteine residues with peptide (2); Mn(ii) accepts additional ligand bonds from the carboxyl γ-O of Asp _4 and Asp _8 to complete the coordination sphere; the unoccupied sites may contain solvent molecules. The failure of Ca(ii) ions to bind to either peptide (1) or (2) appears to result, under our conditions, from the absence of chelating properties in the chosen fragments.
机译:来自PARK9帕金森氏病基因的两个肽序列ProAspGluLysHisGluLeu,(P _1D _2E _3K _4H _5E _6L _7)(1)和PheCysGlyAspGlyAlaAsnAspCysGly(F _1C _2G _A _(_ C _4_D_8_6_(3 _D_D)(3) ii),Zn(ii)和Ca(ii)结合。该片段位于PARK9编码的蛋白质中的残基1165至1171和1184至1193。这种蛋白质可以保护细胞免受锰中毒,锰是造成帕金森氏病样综合征的环境危险因素。一维和二维NMR光谱已用于了解在不同pH值和不同配体与金属摩尔比下金属结合位点的细节。 Mn(ii)和Zn(ii)与肽(1)的配位涉及His _5的咪唑N_ε或N_δ和Asp _2,Glu _3和Glu _6的羧基γ-O。六个供体原子参与Mn(ii)结合,导致扭曲的八面体几何形状,可能涉及羧基的二齿相互作用。四个供体原子参与Zn(ii)结合,形成四配位几何。 Mn(ii)和Zn(ii)的配位涉及带有肽(2)的两个半胱氨酸残基; Mn(ii)从Asp _4和Asp _8的羧基γ-O接受另外的配体键以完成配位球;空位可能包含溶剂分子。在我们的条件下,Ca(ii)离子无法结合肽(1)或(2)的失败似乎是由于所选片段中没有螯合特性而导致的。

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