MarR homologs with urate-binding signature
MarR homologs with urate-binding signature
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DOI：
10.1002/pro.588
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发表时间：
2011-03-01
期刊：
影响因子：
8
通讯作者：
Grove, Anne
中科院分区：
文献类型：
--
作者：
Perera, Inoka C.;Grove, Anne
与活体宿主相关的细菌需要复杂的机制来检测和响应宿主的防御。早期宿主对入侵细菌的部分防御是活性氧的产生，而黄嘌呤氧化酶是这种物质的主要产生者之一。黄嘌呤氧化酶活性的最终产物尿酸盐，先前被证明是耐辐射球菌编码的HucR的天然配体，并且被证明可以减弱农杆菌编码的PecS和泰国伯克霍尔德菌编码的MftR的DNA结合，这些都是多重抗生素耐药调节因子（MarR）家族的成员。我们在这里表明，参与结合尿酸和引发DNA结合拮抗的残基在MarR同源物的特定子集中是保守的。尽管HucR通过调节尿酸酶基因来控制内源性尿酸水平，但几乎所有其他同源物都被预测对外源性尿酸水平做出反应，并调节属于药物代谢物转运蛋白（DMT）或主要促进物超家族（MFS）的跨膜转运蛋白，这进一步证明了同源转录因子在各自启动子区域内存在保守结合位点。这些数据表明同源基因用于不同的调控目的。我们建议将这个独特的MarR同源亚家族命名为UrtR (urate responsive transcriptional regulator)，基于它们共同的urate介导的DNA结合衰减机制。
Bacteria that associate with living hosts require intricate mechanisms to detect and respond to host defenses. Part of the early host defense against invading bacteria is the production of reactive oxygen species, and xanthine oxidase is one of the main producers of such agents. The end-product of the enzymatic activity of xanthine oxidase, urate, was previously shown to be the natural ligand for Deinococcus radiodurans-encoded HucR and it was shown to attenuate DNA binding by Agrobacterium tumefaciens-encoded PecS and Burkholderia thailandensis-encoded MftR, all members of the multiple antibiotic resistance regulator (MarR) family. We here show that residues involved in binding urate and eliciting the DNA binding antagonism are conserved in a specific subset of MarR homologs. Although HucR controls endogenous urate levels by regulating a uricase gene, almost all other homologs are predicted to respond to exogenous urate levels and to regulate a transmembrane transport protein belonging to either the drug metabolite transporter (DMT) or the major facilitator superfamily (MFS), as further evidenced by the presence of conserved binding sites for the cognate transcription factor within the respective promoter regions. These data suggest the use of orthologous genes for different regulatory purposes. We propose the designation UrtR (urate responsive transcriptional regulator) for this distinct subfamily of MarR homologs based on their common mechanism of urate-mediated attenuation of DNA binding.