The Role of Bacillithiol in Gram-Positive Firmicutes.
The Role of Bacillithiol in Gram-Positive Firmicutes.
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DOI：
10.1089/ars.2017.7057
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发表时间：
2018-02-20
影响因子：
6.6
通讯作者：
Helmann JD
中科院分区：
文献类型：
--
作者：
Chandrangsu P;Loi VV;Antelmann H;Helmann JD
意义：自从杆菌硫醇(BSH)的发现和结构鉴定以来，BSH生物合成酶(BSHA/B/C)和依赖于BSH的解毒酶(FosB、Bst、GlxA/B)在芽孢杆菌和葡萄球菌中的生化功能已被研究。结果表明，BSH在活性氧、亲电物种、烷化剂、毒素和抗生素的解毒中起着重要作用。最新进展：最近，BSH在金属稳态(锌缓冲、铁硫簇和铜稳态)和金黄色葡萄球菌毒力控制中的新功能被发现。出乎意料的是，金黄色葡萄球菌NCTC8325谱系的菌株被鉴定为天然的BSH缺陷突变株。现代基于质谱学的方法揭示了在次氯酸盐胁迫下，蛋白质S-杆状硫基化在全球范围内作为一种重要的调节氧化还原修饰。S-OhrR、MEE和甘油醛-3-磷酸脱氢酶(GAP)的杆状硫醇化作用类似于S-谷胱甘肽基化，既是氧化还原调节装置，也是氧化应激下的硫醇保护装置。关键问题：尽管杆菌氧化还蛋白(BRX)途径在逆转S-杆菌硫基化反应中的作用最近已经得到了研究，但要建立完整的BRX还原途径，包括体内氧化的BSH还原的主要酶(S)和BRX作用的靶点，还需要做更多的工作。未来方向：尽管发现了大量的S-杆菌硫化蛋白，但这种氧化还原修饰的生理学意义仅与选定的靶点有关，应该是未来研究的主题。此外，更多的依赖BSH的解毒酶从以前的研究中得到了明显的证据，尽管它们的作用和生化机制需要进一步研究。这篇对BSH研究的综述也为未来的研究指出了这些缺失的空白。抗氧化剂。氧化还原信号。28445-462。
Significance: Since the discovery and structural characterization of bacillithiol (BSH), the biochemical functions of BSH-biosynthesis enzymes (BshA/B/C) and BSH-dependent detoxification enzymes (FosB, Bst, GlxA/B) have been explored in Bacillus and Staphylococcus species. It was shown that BSH plays an important role in detoxification of reactive oxygen and electrophilic species, alkylating agents, toxins, and antibiotics. Recent Advances: More recently, new functions of BSH were discovered in metal homeostasis (Zn buffering, Fe-sulfur cluster, and copper homeostasis) and virulence control in Staphylococcus aureus. Unexpectedly, strains of the S. aureus NCTC8325 lineage were identified as natural BSH-deficient mutants. Modern mass spectrometry-based approaches have revealed the global reach of protein S-bacillithiolation in Firmicutes as an important regulatory redox modification under hypochlorite stress. S-bacillithiolation of OhrR, MetE, and glyceraldehyde-3-phosphate dehydrogenase (Gap) functions, analogous to S-glutathionylation, as both a redox-regulatory device and in thiol protection under oxidative stress. Critical Issues: Although the functions of the bacilliredoxin (Brx) pathways in the reversal of S-bacillithiolations have been recently addressed, significantly more work is needed to establish the complete Brx reduction pathway, including the major enzyme(s), for reduction of oxidized BSH (BSSB) and the targets of Brx action in vivo. Future Directions: Despite the large number of identified S-bacillithiolated proteins, the physiological relevance of this redox modification was shown for only selected targets and should be a subject of future studies. In addition, many more BSH-dependent detoxification enzymes are evident from previous studies, although their roles and biochemical mechanisms require further study. This review of BSH research also pin-points these missing gaps for future research. Antioxid. Redox Signal. 28, 445–462.
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影响因子：
4.1
作者：
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通讯作者：
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影响因子：
3.6
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