Transcriptional regulation of NAD metabolism in bacteria: NrtR family of Nudix-related regulators.
Transcriptional regulation of NAD metabolism in bacteria: NrtR family of Nudix-related regulators.
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DOI：
10.1093/nar/gkn047
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发表时间：
2008-04
影响因子：
14.9
通讯作者：
Raffaelli N
中科院分区：
文献类型：
--
作者：
Rodionov DA;De Ingeniis J;Mancini C;Cimadamore F;Zhang H;Osterman AL;Raffaelli N
通过比较基因组学方法鉴定了一个新的转录因子家族，该家族负责调节广泛细菌中NAD合成的各个方面。该家族的调控因子（这里称为Nudix相关转录调控因子的NrtR）目前被注释为来自Nudix家族的adp核糖焦磷酸酶，由n端Nudix样效应域和c端dna结合hth样结构域组成。通过鉴定和比较分析NAD生物合成途径上游基因的NrtR结合位点，重构了不同细菌基因组中的NrtR调控子。候选的nrtr结合DNA基序在微生物谱系之间显示出显著的差异，尽管它们中的大多数可以追踪到共同的共识序列。生物信息学预测通过凝胶迁移位移测定对两个NrtR家族代表进行了实验验证。adp核糖是NAD糖水解裂解的产物，可以抑制NrtR蛋白与其DNA靶位点的体外结合。除了直接调节NAD稳态的主要作用外，NrtR家族的一些成员似乎还被招募来调节其他代谢途径，包括糖戊糖利用和焦磷酸磷酸核糖基的生物发生。这项工作以及对NiaR调控的相关研究表明，细菌控制NAD代谢途径的调控策略具有显著的可变性。
A novel family of transcription factors responsible for regulation of various aspects of NAD synthesis in a broad range of bacteria was identified by comparative genomics approach. Regulators of this family (here termed NrtR for Nudix-related transcriptional regulators), currently annotated as ADP-ribose pyrophosphatases from the Nudix family, are composed of an N-terminal Nudix-like effector domain and a C-terminal DNA-binding HTH-like domain. NrtR regulons were reconstructed in diverse bacterial genomes by identification and comparative analysis of NrtR-binding sites upstream of genes involved in NAD biosynthetic pathways. The candidate NrtR-binding DNA motifs showed significant variability between microbial lineages, although the common consensus sequence could be traced for most of them. Bioinformatics predictions were experimentally validated by gel mobility shift assays for two NrtR family representatives. ADP-ribose, the product of glycohydrolytic cleavage of NAD, was found to suppress the in vitro binding of NrtR proteins to their DNA target sites. In addition to a major role in the direct regulation of NAD homeostasis, some members of NrtR family appear to have been recruited for the regulation of other metabolic pathways, including sugar pentoses utilization and biogenesis of phosphoribosyl pyrophosphate. This work and the accompanying study of NiaR regulon demonstrate significant variability of regulatory strategies for control of NAD metabolic pathway in bacteria.
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影响因子：
3.2
作者：
Gerdes, SY;Kurnasov, OV;Osterman, AL
通讯作者：
Osterman, AL
DOI：
10.1002/9780470123195.ch5
发表时间：
1999-01-01
期刊：
ADVANCES IN ENZYMOLOGY, VOL 73
影响因子：
--
作者：
Magni, G;Amici, A;Ruggieri, S
通讯作者：
Ruggieri, S
影响因子：
14.9
作者：
Chenna, R;Sugawara, H;Thompson, JD
通讯作者：
Thompson, JD
影响因子：
3.2
作者：
Grose, JH;Bergthorsson, U;Roth, JR
通讯作者：
Roth, JR
DOI：
10.1016/j.bbapap.2004.03.004
发表时间：
2004-06-01
影响因子：
3.2
作者：
Okuda, K;Nishiyama, Y;Hayashi, H
通讯作者：
Hayashi, H