Metal-dependent amyloid β-degrading catalytic antibody construct.
Metal-dependent amyloid β-degrading catalytic antibody construct.
复制标题
金属依赖性淀粉样β 降解催化抗体构建体。
DOI：
10.1016/j.jbiotec.2014.03.026
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发表时间：
2014
影响因子：
4.1
通讯作者：
Paul,Sudhir
中科院分区：
文献类型：
--
作者：
Nishiyama,Yasuhiro;Taguchi,Hiroaki;Hara,Mariko;Planque,StephanieA;Mitsuda,Yukie;Paul,Sudhir
Catalytic antibodies (catabodies) that degrade target antigens rapidly are rare. We describe the metal-dependence of catabody construct 2E6, an engineered heterodimer of immunoglobulin light chain variable domains that hydrolyzes amyloid β peptides (Aβ) specifically. In addition to the electrophilic phosphonate inhibitor of serine proteases, the metal chelators ethylenediaminetetraacetic acid (EDTA) and 1,10-phenanthroline completely inhibited the hydrolysis of Aβ by catabody 2E6. Formation of catabody-electrophilic phosphonate inhibitor adducts was unaffected by EDTA, suggesting that the metal exerts a favorable effect on a catalytic step after the initial catabody nucleophilic attack on Aβ. The EDTA inactivated catabody failed to disaggregate fibrillar Aβ, indicating the functional importance of the Aβ hydrolytic activity. Treating the EDTA-inactivated catabody with Zn2+or Co2+restored the Aβ hydrolytic activity, and Zn2+-induced catabody conformational transitions were evident by fluorescence emission spectroscopy. The studies reveal the absolute catabody dependence on a metal cofactor.
