Focus on phosphoaspartate and phosphoglutamate

Abstract

Protein phosphorylation is a common signalling mechanism in both prokaryotic and eukaryotic organisms. Whilst the focus of protein phosphorylation research has primarily been on protein serine/threonine or tyrosine phosphorylation, there are other phosphoamino acids that are also biologically important. Two of the phosphoamino acids that are functionally involved in the biochemistry of protein phosphorylation and signalling pathways are phosphoaspartate and phosphoglutamate, and this review focuses on their chemistry and biochemistry. In particular, we cover the biological aspects of phosphoaspartate and phosphoglutamate in signalling pathways and as phosphoenzyme intermediates. In addition, we examine the synthesis of both of these phosphoamino acids and the chemistry of the acyl phosphate group. Although phosphoaspartate is a major component of prokaryotic two-component signalling pathways, this review casts its net wider to include reports of phosphoaspartate in eukaryotic cells. Reports of phosphoglutamate, although limited, appear to be more common as free phosphoglutamate than those found in phosphoprotein form.

Strong anion exchange‐mediated phosphoproteomics reveals extensive human non‐canonical phosphorylation

“…Of note, the generation of both site‐specific and generic antibodies against phosphohistidine (pHis) (Kee et al , , ; Fuhs et al , ; Lilley et al , ) has recently allowed mammalian cell‐type independent roles for this PTM to be elucidated (Fuhs et al , ) in processes as diverse as ion channel regulation (Srivastava et al , ) and T‐cell signalling (Panda et al , ), and during cell proliferation, differentiation and migration. In contrast, and despite occasional reports in the literature (Besant et al , ; Attwood et al , ), the prevalence (or otherwise) of other non‐canonical protein phosphorylation events has not been reliably confirmed in human cells, and so specific information about the extent and details of the sites of modification is lacking.…”

A pan-specific antibody for direct detection of protein histidine phosphorylation

“…2 By contrast, there is a dearth of such tools for studying other protein phosphorylation events, a situation which has greatly hindered our understanding of both the extent and functional roles of these more elusive PTMs. 3,4,5 This situation is especially striking for protein histidine phosphorylation, a modification known for 50 years, 6 and whose importance is recognized in processes ranging from central metabolism to signaling in bacteria and lower eukaryotes. 7 It is currently not possible to monitor global pHis levels within a native proteome, something that is now routine for Ser, Thr and Tyr phosphorylation.…”

Site-specific His/Asp phosphoproteomic analysis of prokaryotes reveals putative targets for drug resistance

“…2 and Additional file 1) to assure the presence of critical b-/y-ions to support phosphorylation of only the designated histidine or aspartate residue but none of the other amino acids (i.e. Ser, Thr, Tyr, Arg, Lys, Glu, Cys) [5, 6]. For example, for peptide FSGLIpHQIAK (Fig.…”

“…In bacteria, various amino acid residues within a protein, including serine, threonine, tyrosine, histidine and aspartate, can be modified with a phosphate group [5, 6]. A plethora of data related to serine, threonine and tyrosine phosphorylations have already been reported.…”