Catalysis and allostery in bacterial ATP phosphoribosyltransferases

ATP phosphoribosyltransferase (ATPPRT) catalyses the first reaction of L-histidine biosynthesis: the condensation of ATP and 5-phospho-α-d-ribose 1-pyrophosphate to form N¹-(5-phospho-β-d-ribosyl)-ATP with the release of inorganic pyrophosphate. L-Histidine allosterically inhibits ATPPRT as a mechanism to regulate this energy-intensive pathway in histidine-synthesising organisms, such as bacteria, archaea and plants. Absent in humans and essential in many disease-causing bacteria, such as Mycobacterium tuberculosis and Acinetobacter baumannii, ATPPRT is a promising drug target for novel antibiotic development. Furthermore, ATPPRT is a target of synthetic biology efforts to maximise L-histidine production in bacteria. Here we provide a brief overview of allosteric concepts and review the structure, catalysis and allosteric mechanism of bacterial ATPPRTs, which exist in two forms in nature, a long and a short form. We highlight recent findings on ATPPRT catalysis, allosteric regulation, inhibition and activation, discuss open questions in the field, and possible industrial and biomedical applications.