<p>ATP phosphoribosyltransferase (<db_xref db="EC" dbkey="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 [<cite idref="PUB00028083"/>].<reaction> ATP + 5-phospho-alpha-D-ribose 1-diphosphate = 1-(5-phospho-D-ribosyl)-ATP + diphosphate </reaction>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.</p><p>This entry represents the two forms of ATP phosphoribosyltransferase: 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 [<cite idref="PUB00028139"/>].</p><p>The structures of the long form enzymes from <taxon tax_id="562">Escherichia coli</taxon> (<db_xref db="SWISSPROT" dbkey="P60757"/>) and <taxon tax_id="1773">Mycobacterium tuberculosis</taxon> (<db_xref db="SWISSPROT" dbkey="P60759"/>) have been determined [<cite idref="PUB00022501"/>, <cite idref="PUB00028134"/>]. 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 "periplamsic 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.</p>