Chasing phosphohistidine, an elusive sibling in the phosphoamino acid family.

Chasing phosphohistidine, an elusive sibling in the phosphoamino acid family.
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DOI:
10.1021/cb200445w
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发表时间:
2012-01-20
影响因子:
4
通讯作者:
Muir, Tom W.
Muir, Tom W.
中科院分区:
生物学2区
文献类型:
--
作者:
Kee, Jung-Min;Muir, Tom W.

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今年(2012年)是蛋白质组氨酸磷酸化发现50周年。组氨酸的磷酸化(pHis)现在被广泛认为是原核生物和低等真核生物中信号转导过程的关键。然而,这种修饰在哺乳动物细胞过程中也被越来越广泛地报道,并与某些人类疾病状态如癌症和炎症有关。尽管如此,仍有许多关于哺乳动物细胞生物学中的修饰的作用和程度有待了解。无论是在体外还是在体内,研究pHis在信号传导中的功能作用都非常困难,这主要是由于修饰的化学不稳定性。因此,我们目前长期缺乏研究组氨酸磷酸化的化学和生物化学工具。在这里,我们讨论了与研究pHis的化学生物学相关的挑战,并回顾了最近的进展,这些进展提供了一些希望,期待已久的生化试剂,用于研究这种难以捉摸的翻译后修饰(PTM)可能很快就会出现。
This year (2012) marks the 50th anniversary of the discovery of protein histidine phosphorylation. Phosphorylation of histidine (pHis) is now widely recognized as being critical to signaling processes in prokaryotes and lower eukaryotes. However, the modification is also becoming more widely reported in mammalian cellular processes and implicated in certain human disease states such as cancer and inflammation. Nonetheless, much remains to be understood about the role and extent of the modification in mammalian cell biology. Studying the functional role of pHis in signaling, either in vitro or in vivo, has proven devilishly hard, largely due to the chemical instability of the modification. As a consequence, we are currently handicapped by a chronic lack of chemical and biochemical tools with which to study histidine phosphorylation. Here, we discuss the challenges associated with studying the chemical biology of pHis and review recent progress that offers some hope that long-awaited biochemical reagents for studying this elusive posttranslational modification (PTM) might soon be available.
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