Campylobacter jejuni adenosine triphosphate phosphoribosyltransferase is an active hexamer which is allosterically controlled by the twisting of a regulatory tail

Adenosine triphosphate phosphoribosyltransferase (ATP-PRT) catalyses the first committed step of the histidine biosynthesis in plants and microorganisms. Here we present the functional and structural characterisation of the ATP-PRT from the pathogenic epsilon-proteobacteria Campylobacter jejuni (CjeATP-PRT). This enzyme is a member of the long form (HisGL ) ATP-PRT and is allosterically inhibited by histidine, which binds to a remote regulatory domain, and competitively inhibited by AMP. In the crystalline form CjeATP-PRT was found to adopt two distinctly different hexameric conformations, with an open homohexameric structure observed in the presence of substrate ATP, and a more compact closed form present when inhibitor histidine is bound. CjeATP-PRT was observed to adopt only a hexameric quaternary structure in solution, contradicting previous hypotheses favouring an allosteric mechanism driven by an oligomer equilibrium. Instead, this study supports the conclusion that the ATP-PRT long form hexamer is the active species; the tightening of this structure in response to remote histidine binding results in an inhibited enzyme. This article is protected by copyright. All rights reserved.