Functional and structural characterization of chimeras of a bacterial genotoxin and human type I DNAse.

Functional and structural characterization of chimeras of a bacterial genotoxin and human type I DNAse.
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DOI:
10.1111/j.1574-6968.2008.01457.x
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发表时间:
2009-02
影响因子:
2.1
通讯作者:
Korostoff J
Korostoff J
中科院分区:
生物学4区
文献类型:
--
作者:
DiRienzo JM;Cao L;Volgina A;Bandelac G;Korostoff J

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构建了一种新型细菌基因毒素的cdtB基因和人I型脱氧核糖核酸酶(DNase I)基因组成的嵌合体,其产物的特征在于相对于天然蛋白质的生化和酶性质。cdtB/DNA酶I嵌合体的产物与基因毒素的CdtA和CdtC亚基形成异源三聚体,并且靶向突变增加了杂合蛋白的比活性。活性嵌合基因产物的表达确立了CdtB蛋白是非典型的二价阳离子依赖性核酸内切酶,并证明了基因工程一类新的治疗剂用于抑制癌细胞增殖的潜力。
Chimeras composed of the cdtB gene of a novel bacterial genotoxin and the human type I deoxyribonuclease (DNase I) gene were constructed and their products characterized relative to the biochemical and enzymatic properties of the native proteins. The product of a cdtB/DNase I chimera formed a heterotrimer with the CdtA and CdtC subunits of the genotoxin and targeted mutations increased the specific activity of the hybrid protein. Expression of active chimeric gene products established that the CdtB protein is an atypical divalent cation-dependent endonuclease and demonstrated the potential for genetically engineering a new class of therapeutic agent for inhibiting the proliferation of cancer cells.
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