Recent Updates on Protein N-Phosphoramidate Hydrolases

Abstract

In contrast to well‐recognized protein phosphorylation on the side‐chain oxygen of Ser, Thr, or Tyr residues, analogous phosphoramidation of the nitrogen of His, Lys, and Arg side chains remains much less investigated, mainly due to the instability of post‐translational modifications and technical difficulties involved in their analysis. For example, reports on the enzyme activities responsible for the formation and hydrolysis of these phosphoramidates date back to as early as the 1950s, but some of these enzymes have only recently been identified and functionally characterized; this has been aided by the development of novel research tools. In this review, we summarize current knowledge of the enzymes that hydrolyze protein N‐phosphoramidates, in terms of their structure, activities, and biological functions, as well as the chemical tools used to investigate them.