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 N 1 ‐(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.