Allosteric Modulation of the Faecalibacterium prausnitzii Hepatitis Delta Virus-like Ribozyme by Glucosamine 6-Phosphate: The Substrate of the Adjacent Gene Product.
Allosteric Modulation of the Faecalibacterium prausnitzii Hepatitis Delta Virus-like Ribozyme by Glucosamine 6-Phosphate: The Substrate of the Adjacent Gene Product.
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葡萄糖6-磷酸葡萄糖的粪便核杆菌肝炎病毒样核酶的变构调节：相邻基因产物的底物。
DOI：
10.1021/acs.biochem.7b00879
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发表时间：
2017-11-14
期刊：
影响因子：
2.9
通讯作者：
Lupták A
中科院分区：
文献类型：
--
作者：
Passalacqua LFM;Jimenez RM;Fong JY;Lupták A
自裂解核酶是在30年前发现的，从细菌到动物，在自然界都有发现，但人们对它们的生物学功能和调节知之甚少，特别是辅因子和代谢物如何改变它们的活性。丁型肝炎病毒样的自切割核酶位于人类肠道细菌普氏杆菌基因组中磷酸氨基葡萄糖变位酶(GLMM)开放阅读框架的上游。在GlmM的非翻译区存在核酶，这表明了基因表达的调节机制。在细菌氨基己糖的生物合成途径中，GlmM酶催化氨基葡萄糖6-磷酸异构化为氨基葡萄糖1-磷酸。在这项研究中，我们研究了这些代谢物对核酶共转录自裂解率的影响。我们的结果表明，氨基葡萄糖6-磷酸，而不是氨基葡萄糖1-磷酸，是一种变构配体，它增加了dRZ-Fpra-1的自裂速率，这提供了第一个已知的例子，即相邻基因产物的底物对自裂解核酶进行变构调节。鉴于核酶是由glmM底物激活的，而不是由产物激活的，这种变构调节可能代表了细菌基因表达调控的一种潜在的前馈机制。
Self-cleaving ribozymes were discovered 30 years ago and have been found throughout nature, from bacteria to animals, but little is known about their biological functions and regulation, particularly how cofactors and metabolites alter their activity. A hepatitis delta virus-like self-cleaving ribozyme maps upstream of a phosphoglucosamine mutase (glmM) open reading frame in the genome of the human gut bacterium Faecalibacterium prausnitzii. The presence of a ribozyme in the untranslated region of glmM suggests a regulation mechanism of gene expression. In the bacterial hexosamine biosynthesis pathway, the enzyme glmM catalyzes the isomerization of glucosamine 6-phosphate into glucosamine 1-phosphate. In this study, we investigated the effect of these metabolites on the co-transcriptional self-cleavage rate of the ribozyme. Our results suggest that glucosamine 6-phosphate, but not glucosamine 1-phosphate, is an allosteric ligand that increases the self-cleavage rate of drz-Fpra-1, providing the first known example of allosteric modulation of a self-cleaving ribozyme by the substrate of the adjacent gene product. Given that the ribozyme is activated by the glmM substrate, but not the product, this allosteric modulation may represent a potential feed-forward mechanism of gene expression regulation in bacteria.
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影响因子：
14.8
作者：
Bingaman JL;Zhang S;Stevens DR;Yennawar NH;Hammes-Schiffer S;Bevilacqua PC
通讯作者：
Bevilacqua PC
影响因子：
16
作者：
Celesnik, Helena;Deana, Atilio;Belasco, Joel G.
通讯作者：
Belasco, Joel G.
影响因子：
15
作者：
Cerrone-Szakal, Andrea L.;Siegfried, Nathan A.;Bevilacqua, Philip C.
通讯作者：
Bevilacqua, Philip C.
影响因子：
64.8
作者：
BUZAYAN, JM;GERLACH, WL;BRUENING, G
通讯作者：
BRUENING, G
识别肝炎三角洲病毒核酶中的催化mg²⁺离子。
影响因子：
2.9
作者：
Chen J;Ganguly A;Miswan Z;Hammes-Schiffer S;Bevilacqua PC;Golden BL
通讯作者：
Golden BL