Formaldehyde reacts with N-terminal proline residues to give bicyclic aminals.
Formaldehyde reacts with N-terminal proline residues to give bicyclic aminals.
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DOI：
10.1038/s42004-022-00801-5
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发表时间：
2023-01-13
影响因子：
5.9
通讯作者：
Schofield, Christopher J.
中科院分区：
文献类型：
--
作者：
John, Tobias;Pires, Elisabete;Hester, Svenja S.;Salah, Eidarus;Hopkinson, Richard J.;Schofield, Christopher J.
甲醛（HCHO）是一种有效的亲电试剂，其毒性超过阈值水平，但也可通过脱甲基酶在真核细胞的细胞核中产生。我们报告了四种典型的人类组蛋白的研究，揭示了组蛋白H2 B与HCHO反应，包括由组蛋白去甲基化酶产生的反应，得到稳定的产物。NMR研究表明，HCHO与H2 B的N-末端脯氨酸和相关酰胺反应，得到5，5-双环缩醛胺，其相对稳定，可与HCHO清除剂竞争。虽然组蛋白修饰的作用，这个反应需要进一步的调查，我们证明了潜在的N-末端缩醛胺的形成，以调节蛋白质的功能进行生化和细胞研究的影响，甲醛催化4-α-巴豆酸互变异构酶，采用亲核的N-末端脯氨酸。结果表明，反应的N-末端残基与甲醛和其他醛有可能改变蛋白质的功能。甲醛在高浓度下是一种有效的有毒亲电体;然而，其潜在的调节作用仍然未知。在这里，作者报告说，甲醛可以与末端含脯氨酸的蛋白质反应，产生稳定的5，5-双环缩醛胺末端，调节蛋白质功能。
Formaldehyde (HCHO) is a potent electrophile that is toxic above threshold levels, but which is also produced in the nuclei of eukaryotic cells by demethylases. We report studies with the four canonical human histones revealing that histone H2B reacts with HCHO, including as generated by a histone demethylase, to give a stable product. NMR studies show that HCHO reacts with the N-terminal proline and associated amide of H2B to give a 5,5-bicyclic aminal that is relatively stable to competition with HCHO scavengers. While the roles of histone modification by this reaction require further investigation, we demonstrated the potential of N-terminal aminal formation to modulate protein function by conducting biochemical and cellular studies on the effects of HCHO on catalysis by 4-oxalocrotonate tautomerase, which employs a nucleophilic N-terminal proline. The results suggest that reactions of N-terminal residues with HCHO and other aldehydes have potential to alter protein function. Formaldehyde is a potent toxic electrophile at high concentrations; however its potential regulatory roles remain unknown. Here, the authors report that formaldehyde can react with terminal proline-containing proteins to generate stable 5,5-bicyclic aminal termini that modulate protein function.
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影响因子：
5.9
作者：
Pietzke, Matthias;Burgos-Barragan, Guillermo;Wit, Niek;Tait-Mulder, Jacqueline;Sumpton, David;Mackay, Gillian M.;Patel, Ketan J.;Vazquez, Alexei
通讯作者：
Vazquez, Alexei
影响因子：
8
作者：
Luka, Zigmund;Pakhomova, Svetlana;Wagner, Conrad
通讯作者：
Wagner, Conrad
影响因子：
3.2
作者：
Hopkinson, Richard J.;Barlow, Philippa S.;Claridge, Timothy D. W.
通讯作者：
Claridge, Timothy D. W.
影响因子：
2.9
作者：
MCGHEE, JD;HIPPEL, PHV
通讯作者：
HIPPEL, PHV
影响因子：
--
作者：
FISHER, AA;KANOF, NB;BIONDI, EM
通讯作者：
BIONDI, EM