Cysteine sulfur chemistry in transcriptional regulators at the host-bacterial pathogen interface.
Cysteine sulfur chemistry in transcriptional regulators at the host-bacterial pathogen interface.
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DOI：
10.1021/acs.biochem.5b00085
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发表时间：
2015-05
期刊：
影响因子：
2.9
通讯作者：
J. Luebke;D. Giedroc
中科院分区：
文献类型：
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作者：
J. Luebke;D. Giedroc
作为宿主-细菌病原体界面的一个组成部分，细菌病原体使用无数的武器来对抗入侵的微生物。该界面由高度反应性的小分子主导，这些小分子共同诱导氧化应激。成功的病原体采用转录调节蛋白，其直接或间接地通过改变还原的低分子量（LMW）硫醇与氧化的低分子量（LMW）硫醇的比率来感测这些小分子，所述还原的低分子量（LMW）硫醇共同构成细胞质中的氧化还原缓冲液。这些转录调节因子采用辅基或反应性半胱氨酸残基来影响编码解毒和修复系统的基因转录的变化，所述解毒和修复系统由高亲和力和低亲和力DNA结合状态之间的调节因子构象转换驱动。半胱氨酸具有高度可极化的硫原子，在氧化应激反应中容易发生氧化态变化，产生一系列调节性翻译后修饰（PTM），包括亚磺酰化（S-羟基化）、与LMW硫醇形成混合二硫键（S-硫醇化）、二硫键和三硫键形成、S-亚硝化和S-烷基化。在这里，我们讨论了几个例子的结构特征的半胱氨酸巯基特异性转录调节剂，感测细胞氧化还原平衡的变化，专注于半胱氨酸PTM本身的性质和小分子氧化应激在介导特定的转录反应的相互作用。
Hosts employ myriad weapons to combat invading microorganisms as an integral feature of the host-bacterial pathogen interface. This interface is dominated by highly reactive small molecules that collectively induce oxidative stress. Successful pathogens employ transcriptional regulatory proteins that sense these small molecules directly or indirectly via a change in the ratio of reduced to oxidized low-molecular weight (LMW) thiols that collectively comprise the redox buffer in the cytoplasm. These transcriptional regulators employ either a prosthetic group or reactive cysteine residue(s) to effect changes in the transcription of genes that encode detoxification and repair systems that is driven by regulator conformational switching between high-affinity and low-affinity DNA-binding states. Cysteine harbors a highly polarizable sulfur atom that readily undergoes changes in oxidation state in response to oxidative stress to produce a range of regulatory post-translational modifications (PTMs), including sulfenylation (S-hydroxylation), mixed disulfide bond formation with LMW thiols (S-thiolation), di- and trisulfide bond formation, S-nitrosation, and S-alkylation. Here we discuss several examples of structurally characterized cysteine thiol-specific transcriptional regulators that sense changes in cellular redox balance, focusing on the nature of the cysteine PTM itself and the interplay of small molecule oxidative stressors in mediating a specific transcriptional response.