ATP phosphoribosyltransferase (2.4.2.17) is the enzyme that catalyzes the first step in the biosynthesis of histidine in bacteria, fungi and plants as shown below. It is a member of the larger phosphoribosyltransferase superfamily of enzymes which catalyse the condensation of 5-phospho-alpha-D-ribose 1-diphosphate with nitrogenous bases in the presence of divalent metal ions [1].

Histidine biosynthesis is an energetically expensive process and ATP phosphoribosyltransferase activity is subject to control at several levels. Transcriptional regulation is based primarily on nutrient conditions and determines the amount of enzyme present in the cell, while feedback inihibition rapidly modulates activity in response to cellular conditions. The enzyme has been shown to be inhibited by 1-(5-phospho-D-ribosyl)-ATP, histidine, ppGpp (a signal associated with adverse environmental conditions) and ADP and AMP (which reflect the overall energy status of the cell). As this pathway of histidine biosynthesis is present only in prokayrotes, plants and fungi, this enzyme is a promising target for the development of novel antimicrobial compounds and herbicides.

This entry represents the C-terminal portion of ATP phosphoribosyltransferase. The enzyme itself exists in equilibrium between an active dimeric form, an inactive hexameric form and higher aggregates [2, 3]. Interconversion between the various forms is largely reversible and is influenced by the binding of the natural substrates and inhibitors of the enzyme. This domain is not directly involved in catalysis but appears to be responsible for the formation of hexamers induced by the binding of inhibitors to the enzyme, thus regulating activity.

1. The PRT protein family. Curr. Opin. Struct. Biol. 11, 733-9
2. The structure of Escherichia coli ATP-phosphoribosyltransferase: identification of substrate binding sites and mode of AMP inhibition. J. Mol. Biol. 336, 131-44
3. Crystal structure of ATP phosphoribosyltransferase from Mycobacterium tuberculosis. J. Biol. Chem. 278, 8333-9

ATP phosphoribosyltransferase (Show more...

Download genes (select columns to include)