Luebke Justin L, Giedroc David P
Department of Chemistry, Indiana University, Bloomington, Indiana 47405-7102, United States.
Biochemistry. 2015 Jun 2;54(21):3235-49. doi: 10.1021/acs.biochem.5b00085. Epub 2015 May 20.
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.
宿主会运用多种武器来对抗入侵的微生物，这是宿主与细菌病原体相互作用界面的一个重要特征。这个界面由高反应性小分子主导，这些小分子共同引发氧化应激。成功的病原体利用转录调节蛋白，这些蛋白通过感知还原型与氧化型低分子量（LMW）硫醇比例的变化来直接或间接检测这些小分子，这些硫醇共同构成了细胞质中的氧化还原缓冲液。这些转录调节因子利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变化，这种变化由调节因子在高亲和力和低亲和力DNA结合状态之间的构象转换驱动。半胱氨酸含有一个高度可极化的硫原子，它会响应氧化应激而容易发生氧化态变化，从而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，我们讨论几个结构特征明确的半胱氨酸硫醇特异性转录调节因子的例子，这些因子感知细胞氧化还原平衡的变化，重点关注半胱氨酸PTM本身的性质以及小分子氧化应激源在介导特定转录反应中的相互作用。
