InterPro: IPR013820 ATP phosphoribosyltransferase, catalytic domain

ATP phosphoribosyltransferase (EC: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].

ATP + 5-phospho-alpha-D-ribose 1-diphosphate = 1-(5-phospho-D-ribosyl)-ATP + diphosphate

ATP phosphoribosyltransferase is found in two distinct forms: a long form containing two catalytic domains and a C-terminal regulatory domain, and a short form in which the regulatory domain is missing. The long form is catalytically competent, but in organisms with the short form, a histidyl-tRNA synthetase paralogue, HisZ, is required for enzyme activity [2]. This entry represents the catalytic region of this enzyme.

The structures of the long form enzymes from Escherichia coli (P60757) and Mycobacterium tuberculosis (P60759) have been determined [3, 4]. The enzyme itself exists in equilibrium between an active dimeric form, an inactive hexameric form and higher aggregates. Interconversion between the various forms is largely reversible and is influenced by the binding of the natural substrates and inhibitors of the enzyme. The two catalytic domains are linked by a two-stranded beta-sheet and togther form a "periplasmic binding protein fold". A crevice between these domains contains the active site. The C-terminal domain is not directly involved in catalysis but appears to be involved the formation of hexamers, induced by the binding of inhibitors such as histidine to the enzyme, thus regulating activity.