Department of Chemistry, Princeton University, New Jersey 08544, United States.
ACS Chem Biol. 2012 Jan 20;7(1):44-51. doi: 10.1021/cb200445w. Epub 2011 Dec 9.
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.
今年（2012 年）标志着蛋白质组氨酸磷酸化发现 50 周年。组氨酸磷酸化（pHis）现已被广泛认为对原核生物和低等真核生物的信号转导过程至关重要。然而，这种修饰在哺乳动物细胞过程中也越来越多地被报道，并与某些人类疾病状态如癌症和炎症有关。尽管如此，关于这种修饰在哺乳动物细胞生物学中的作用和程度，仍有许多需要了解。研究 pHis 在信号转导中的功能作用，无论是在体外还是体内，都被证明非常困难，主要是由于修饰的化学不稳定性。因此，我们目前受到缺乏研究组氨酸磷酸化的化学和生化工具的严重制约。在这里，我们讨论了研究 pHis 化学生物学相关的挑战，并回顾了最近的进展，这些进展为研究这种难以捉摸的翻译后修饰（PTM）的生化试剂可能很快就会问世带来了一些希望。
