Metabolic and Structural Insights into Hydrogen Sulfide Mis-Regulation in Enterococcus faecalis.
Metabolic and Structural Insights into Hydrogen Sulfide Mis-Regulation in Enterococcus faecalis.
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DOI：
10.3390/antiox11081607
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发表时间：
2022-08-19
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影响因子：
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硫化氢（H2S）是一种细胞保护剂，细菌在响应宿主诱导的应激源（如氧化应激和抗生素）时使用。然而，通常归因于H2S的生理益处可能是下游的硫的更多氧化形式的结果，统称为活性硫物质（RSS），包括有机过硫化物（RSSH）。在这里，我们研究了肠道微生物粪肠球菌对外源性Na 2S作为H2S/RSS毒性的代表的代谢反应。我们发现，外源硫化物增加蛋白质丰度的酶负责辅酶A（CoA）的生物合成。蛋白质组S-硫化（过硫化），一种与H2S信号转导有关的翻译后修饰，也广泛存在于这种生物体中，并通过CstR、RSS传感器、辅酶A过硫化物（CoASSH）还原酶（CoAPR）和与从头脂肪酸生物合成和乙酰辅酶A合成相关的酶中的外源性硫化物显著升高。外源性硫化物显着影响脂肪酸的形态以及乙酰辅酶A的细胞浓度，这表明蛋白质过硫化可能会影响通过这些途径的流量。事实上，CoASSH是E. faecalis磷酸转乙酰酶（Pta），这表明H2S/RSS水平增加的重要代谢结果可能是该关键代谢物的过硫化，其反过来抑制CoA和酰基-CoA利用酶。我们的CoA结合CoAPR的2.05 μ m晶体结构为大肠杆菌中CoASSH清除提供了新的结构见解。粪便。
Hydrogen sulfide (H2S) is implicated as a cytoprotective agent that bacteria employ in response to host-induced stressors, such as oxidative stress and antibiotics. The physiological benefits often attributed to H2S, however, are likely a result of downstream, more oxidized forms of sulfur, collectively termed reactive sulfur species (RSS) and including the organic persulfide (RSSH). Here, we investigated the metabolic response of the commensal gut microorganism Enterococcus faecalis to exogenous Na2S as a proxy for H2S/RSS toxicity. We found that exogenous sulfide increases protein abundance for enzymes responsible for the biosynthesis of coenzyme A (CoA). Proteome S-sulfuration (persulfidation), a posttranslational modification implicated in H2S signal transduction, is also widespread in this organism and is significantly elevated by exogenous sulfide in CstR, the RSS sensor, coenzyme A persulfide (CoASSH) reductase (CoAPR) and enzymes associated with de novo fatty acid biosynthesis and acetyl-CoA synthesis. Exogenous sulfide significantly impacts the speciation of fatty acids as well as cellular concentrations of acetyl-CoA, suggesting that protein persulfidation may impact flux through these pathways. Indeed, CoASSH is an inhibitor of E. faecalis phosphotransacetylase (Pta), suggesting that an important metabolic consequence of increased levels of H2S/RSS may be over-persulfidation of this key metabolite, which, in turn, inhibits CoA and acyl-CoA-utilizing enzymes. Our 2.05 Å crystallographic structure of CoA-bound CoAPR provides new structural insights into CoASSH clearance in E. faecalis.
DOI：
10.1155/2021/8817136
发表时间：
2021
期刊：
Archaea (Vancouver, B.C.)
影响因子：
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作者：
Shabdar S;Anaclet B;Castineiras AG;Desir N;Choe N;Crane EJ 3rd;Sazinsky MH
通讯作者：
Sazinsky MH