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正交核苷激酶的计算设计。

Computational design of orthogonal nucleoside kinases.

机构信息

Department of Chemistry, Emory University, Atlanta, GA 30322, USA.

出版信息

Chem Commun (Camb). 2010 Dec 14;46(46):8803-5. doi: 10.1039/c0cc02961k. Epub 2010 Oct 19.

DOI:10.1039/c0cc02961k
PMID:20959903
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3733048/
Abstract

We report the computational enzyme design of an orthogonal nucleoside analog kinase for 3'-deoxythymidine. The best kinase variant shows an 8500-fold change in substrate specificity, resulting from a 4.6-fold gain in catalytic efficiency for the nucleoside analog and a 2000-fold decline for the native substrate thymidine.

摘要

我们报告了一种用于 3'-脱氧胸苷的正交核苷类似物激酶的计算酶设计。最佳激酶变体显示出 8500 倍的底物特异性变化,这是由于核苷类似物的催化效率提高了 4.6 倍,而天然底物胸苷的活性降低了 2000 倍。

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本文引用的文献

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J Med Chem. 2010 Jan 28;53(2):521-38. doi: 10.1021/jm900492g.
2
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Nucleic Acids Res. 2009 Jul;37(13):4472-81. doi: 10.1093/nar/gkp400. Epub 2009 May 27.
3
Alteration of enzyme specificity by computational loop remodeling and design.通过计算循环重塑和设计改变酶的特异性。
Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9215-20. doi: 10.1073/pnas.0811070106. Epub 2009 May 21.
4
Macromolecular modeling with rosetta.使用Rosetta进行大分子建模。
Annu Rev Biochem. 2008;77:363-82. doi: 10.1146/annurev.biochem.77.062906.171838.
5
Enhanced toxicity of purine nucleoside analogs in cells expressing Drosophila melanogaster nucleoside kinase mutants.嘌呤核苷类似物在表达黑腹果蝇核苷激酶突变体的细胞中增强的毒性。
Gene Ther. 2007 Jan;14(1):86-92. doi: 10.1038/sj.gt.3302835. Epub 2006 Aug 3.
6
A statistical analysis of random mutagenesis methods used for directed protein evolution.用于定向蛋白质进化的随机诱变方法的统计分析。
J Mol Biol. 2006 Jan 27;355(4):858-71. doi: 10.1016/j.jmb.2005.10.082. Epub 2005 Nov 17.
7
Computational thermostabilization of an enzyme.酶的计算热稳定性
Science. 2005 May 6;308(5723):857-60. doi: 10.1126/science.1107387.
8
DNA precursor asymmetries in mammalian tissue mitochondria and possible contribution to mutagenesis through reduced replication fidelity.哺乳动物组织线粒体中的DNA前体不对称性及其通过降低复制保真度对诱变的可能贡献。
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