Focus on phosphohistidine

  title={Focus on phosphohistidine},
  author={Paul V. Attwood and Matthew J. Piggott and Xin Lin Zu and Paul G. Besant},
  journal={Amino Acids},
Summary.Phosphohistidine has been identified as an enzymic intermediate in numerous biochemical reactions and plays a functional role in many regulatory pathways. Unlike the phosphoester bond of its cousins (phosphoserine, phosphothreonine and phosphotyrosine), the phosphoramidate (P–N) bond of phosphohistidine has a high ΔG° of hydrolysis and is unstable under acidic conditions. This acid-lability has meant that the study of protein histidine phosphorylation and the associated protein kinases… 
Chasing phosphohistidine, an elusive sibling in the phosphoamino acid family.
The challenges associated with studying the chemical biology of pHis are discussed and recent progress is reviewed that offers some hope that long-awaited biochemical reagents for studying this elusive posttranslational modification (PTM) might soon be available.
Focus on phosphoaspartate and phosphoglutamate
This review covers the biological aspects of phosphoaspartate and phosphoglutamate in signalling pathways and as phosphoenzyme intermediates and examines the synthesis of both of these phosphoamino acids and the chemistry of the acyl phosphate group.
Advances in development of new tools for the study of phosphohistidine
This review highlights some misinterpretations that have arisen in the existing literature, pinpoints outstanding questions and potential future directions to clarify the role of pHis in mammalian signalling systems, and places particular emphasis on pHis isomerization and the hybrid functionality for both pHis and pTyr of the proposed τ-pHis analogue bearing the triazole residue.
Focus on phosphoarginine and phospholysine.
This review focuses on the biological aspects of phosphoarginine as a means of storing and using metabolic energy (in place of phosphocreatine in invertebrates), the chemistrybehind its synthesis and the chemistry behind its highenergy phosphoramidate bond.
The phosphohistidine phosphatase SixA dephosphorylates the phosphocarrier NPr
The widespread conservation of SixA, and its coincidence with the phosphotransferase system studied here, suggests that this dephosphorylation mechanism may be conserved in other bacteria.
Prospects for stable analogues of phosphohistidine.
The present short review highlights the chemical challenges that this modification presents and the manner in which chemical synthesis has been used to identify and mimic the modification in proteins.
The many ways that nature has exploited the unusual structural and chemical properties of phosphohistidine for use in proteins.
The varied roles of pHis-containing proteins are examined from a chemical and structural perspective, and an overview of recent developments in pHis proteomics and antibody development is presented.
Histidine kinases and the missing phosphoproteome from prokaryotes to eukaryotes
The role that the NM23/NME/NDPK phosphotransferase has, how the addition of the pHis phosphoproteome will expand the phosphoproteinome and make His phosphorylation part of the global phosphorylated world are discussed, and the study of NM23 histidine kinase is highlighted as an entrée into the world of histidineosphorylation.
Histidine phosphorylation in metalloprotein binding sites.
P-N bond protein phosphatases.
  • P. Attwood
  • Biology
    Biochimica et biophysica acta
  • 2013


Phosphorylation and dephosphorylation of histidine residues in proteins.
This minireview briefly summarizes the extensive knowledge of the key mechanisms and functions of phosphohistidine in bacteria and describes the still limited, yet increasing, data from homologs of the bacterial two-component system.
Protein histidine phosphorylation: Increased stability of thiophosphohistidine
By replacing the phosphate linked to the histidine residue with a thiophosphate, a phosphohistidine derivative with increased stability is formed, which allows the analysis of phosphohistsidine‐containing proteins by established biochemical techniques and will greatly aid in the investigation of the role of this posttranslational modification in cellular processes.
Mammalian histidine kinases.
Phosphohistidyl active sites in polyphosphate kinase of Escherichia coli.
Of the 16 histidine residues in PPK of E. coli, 4 are conserved among several bacterial species, and mutagenesis shows that two are unaffected in function when mutated to glutamine, whereas two others fail to be phosphorylated, show no enzymatic activities, and fail to support polyP accumulation in cells bearing these mutant enzymes.
The preparation and characterization of phosphorylated derivatives of histidine.
  • D. Hultquist
  • Chemistry, Biology
    Biochimica et biophysica acta
  • 1968
Characterization of the 1-phosphohistidinyl residue in the phosphocarrier protein HPr of the phosphoenolpyruvate: sugar phosphotransferase system of Streptococcus faecalis.
The results suggest that a similar carboxyl group is present at the active site in HPr from Streptococcus faecalis, and it is now known that in HPR from Escherichia coli the C-terminal residue Glu-85 is present.
Mammalian protein histidine kinases.
Phosphorylation of histidine in proteins by a nuclear extract of Physarum polycephalum plasmodia.
The data show that Physarum nuclei contain a major kinase activity which produces phosphohistidine, which provides the basis for a complete characterization of the structure and function of thephysarum enzyme and can be applied to the study of similar kinase activities in other systems.
Phosphofurylalanine, a stable analog of phosphohistidine.
Autophosphorylation of nucleoside diphosphate kinase from Myxococcus xanthus
Results suggest that the phosphohistidine intermediate is formed at this residue during the transphosphorylation reaction from nucleoside triphosphates to nucleosides diphosphates.