Binding Selectivity of Methanobactin from Methylosinus trichosporium OB3b for Copper(I), Silver(I), Zinc(II), Nickel(II), Cobalt(II), Manganese(II), Lead(II), and Iron(II)
Binding Selectivity of Methanobactin from Methylosinus trichosporium OB3b for Copper(I), Silver(I), Zinc(II), Nickel(II), Cobalt(II), Manganese(II), Lead(II), and Iron(II)
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DOI：
10.1007/s13361-017-1778-9
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发表时间：
2017-08
影响因子：
3.2
通讯作者：
J. McCabe;Rajpal Vangala;L. Angel
中科院分区：
文献类型：
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作者：
J. McCabe;Rajpal Vangala;L. Angel
甲烷氧化菌素（Methylosinus trichosporium，Mb）是产甲烷细菌中一类金属结合肽。Mb将选择性地结合Cu（II）并将其还原为Cu（I），并且被认为介导甲烷单加氧酶的铜辅因子的获得。Mb的这些铜螯合性质使其潜在地可用作螯合剂，用于治疗其中铜起作用的疾病，包括威尔逊病、癌症和神经变性疾病。利用行波离子迁移质谱（TWIMS），通过一系列金属离子滴定、pH滴定和金属离子置换滴定，确定了Ag（I）、Pb（II）、Co（II）、Fe（II）、Mn（II）、Ni（II）和Zn（II）对Mb铜结合位点的竞争。TWIMS分析允许在滴定过程中存在的所有单个Mb种类的明确鉴定和定量，并测量它们的碰撞截面和碰撞诱导解离模式。结果表明，Ag（I）和Ni（II）与Mb的结合是不可逆的，不能被Cu（I）有效置换，而Ag（I）也能部分置换Mb络合物中的Cu（I）。在pH = 6.5时，Mb结合选择性的顺序为Ag（I）> Cu（I）>Ni（II）> Zn（II）>Co（II）>>Mn（II）> Pb（II）>Fe（II）;在pH = 7.5 ~ 10.4时，Mb结合选择性的顺序为Ag（I）>Cu（I）>Ni（II）>Co（II）>Zn（II）>Mn（II）> Pb（II）>Fe（II）。二硫键还原的Cu（I）和Ag（I）配合物的击穿曲线表明，它们的相对稳定性与它们的CCS所指示的紧凑折叠结构之间存在相关性。荧光光谱法，这使得确定的结合常数，比较以及与TWIMS分析，除了镍（II）络合物。
Methanobactin (Mb) fromMethylosinus trichosporiumOB3b is a member of a class of metal binding peptides identified in methanotrophic bacteria. Mb will selectively bind and reduce Cu(II) to Cu(I), and is thought to mediate the acquisition of the copper cofactor for the enzyme methane monooxygenase. These copper chelating properties of Mb make it potentially useful as a chelating agent for treatment of diseases where copper plays a role including Wilson’s disease, cancers, and neurodegenerative diseases. Utilizing traveling wave ion mobility-mass spectrometry (TWIMS), the competition for the Mb copper binding site from Ag(I), Pb(II), Co(II), Fe(II), Mn(II), Ni(II), and Zn(II) has been determined by a series of metal ion titrations, pH titrations, and metal ion displacement titrations. The TWIMS analyses allowed for the explicit identification and quantification of all the individual Mb species present during the titrations and measured their collision cross-sections and collision-induced dissociation patterns. The results showed Ag(I) and Ni(II) could irreversibly bind to Mb and not be effectively displaced by Cu(I), whereas Ag(I) could also partially displace Cu(I) from the Mb complex. At pH ≈ 6.5, the Mb binding selectivity follows the order Ag(I)≈Cu(I)>Ni(II)≈Zn(II)>Co(II)>>Mn(II)≈Pb(II)>Fe(II), and at pH 7.5 to 10.4 the order is Ag(I)>Cu(I)>Ni(II)>Co(II)>Zn(II)>Mn(II)≈Pb(II)>Fe(II). Breakdown curves of the disulfide reduced Cu(I) and Ag(I) complexes showed a correlation existed between their relative stability and their compact folded structure indicated by their CCS. Fluorescence spectroscopy, which allowed the determination of the binding constant, compared well with the TWIMS analyses, with the exception of the Ni(II) complex.