AlloRep: A Repository of Sequence, Structural and Mutagenesis Data for the LacI/GalR Transcription Regulators.

AlloRep: A Repository of Sequence, Structural and Mutagenesis Data for the LacI/GalR Transcription Regulators.
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AlloRep:LacI/GalR 转录调节因子的序列、结构和诱变数据存储库。

DOI:
10.1016/j.jmb.2015.09.015
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发表时间:
2016
影响因子:
5.6
通讯作者:
Swint-Kruse,Liskin
Swint-Kruse,Liskin
中科院分区:
生物学2区
文献类型:
--
作者:
Sousa,FilipaL;Parente,DanielJ;Shis,DavidL;Hessman,JacobA;Chazelle,Allen;Bennett,MatthewR;Teichmann,SarahA;Swint-Kruse,Liskin

文献摘要

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蛋白质家族通过在功能重要的氨基酸位置积累点突变来进化功能变异。转录调节因子的LacI/GalR家族中的同源物已经进化为结合不同的DNA序列和变构调节分子。除了在细菌代谢中发挥关键作用外,这些蛋白质还被广泛用作基准结构和功能预测算法的模型家族。我们已经收集了> 3000个序列的人工序列比对,> 5750个LacI/GalR突变变体的体内表型和生化数据,以及65个LacI/GalR同源结构的非共价残基接触网络。利用这一丰富的数据资源,我们比较了非共价残基接触网络的LacI/GalR亚家族的设计和实验验证变构突变体的合成LacI/GalR阻遏物用于生物技术。AlloRep数据库(可在www.AlloRep.org免费获得)是未来LacI/GalR同系物进化研究和功能变化基准计算预测的关键资源。
Protein families evolve functional variation by accumulating point mutations at functionally important amino acid positions. Homologs in the LacI/GalR family of transcription regulators have evolved to bind diverse DNA sequences and allosteric regulatory molecules. In addition to playing key roles in bacterial metabolism, these proteins have been widely used as a model family for benchmarking structural and functional prediction algorithms. We have collected manually curated sequence alignments for > 3000 sequences,in vivophenotypic and biochemical data for > 5750 LacI/GalR mutational variants, and noncovalent residue contact networks for 65 LacI/GalR homolog structures. Using this rich data resource, we compared the noncovalent residue contact networks of the LacI/GalR subfamilies to design and experimentally validate an allosteric mutant of a synthetic LacI/GalR repressor for use in biotechnology. The AlloRep database (freely available at www.AlloRep.org) is a key resource for future evolutionary studies of LacI/GalR homologs and for benchmarking computational predictions of functional change.