title: Campylobacter jejuni adenosine triphosphate phosphoribosyltransferase is an active hexamer that is allosterically controlled by the twisting of a regulatory tail.
abstract: Adenosine triphosphate phosphoribosyltransferase (ATP-PRT) catalyzes the first committed step of the histidine biosynthesis in plants and microorganisms. Here, we present the functional and structural characterization of the ATP-PRT from the pathogenic ε-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 favoring 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.
authors.affiliation: Maurice Wilkins Centre, Biomolecular Interaction Centre, Christchurch, 8140, New Zealand.|Department of Chemistry, University of Canterbury, Christchurch, 8140, New Zealand.
authors.forename: Gerd
authors.initials: G
authors.lastname: Mittelstädt
authors.affiliation: Maurice Wilkins Centre, Biomolecular Interaction Centre, Christchurch, 8140, New Zealand.|Department of Chemistry, University of Canterbury, Christchurch, 8140, New Zealand.
authors.forename: Gert-Jan
authors.initials: GJ
authors.lastname: Moggré
authors.affiliation: Australian Synchrotron, Clayton, Melbourne, Victoria, 3168, Australia.|Department of Biochemistry and Molecular Biology, Monash University, Clayton, Campus, Melbourne, Victoria, 3800, Australia.
authors.forename: Santosh
authors.initials: S
authors.lastname: Panjikar
authors.affiliation: Biomolecular Interaction Centre and School of Biological Sciences, University of Canterbury, Christchurch, 8140, New Zealand.
authors.forename: Ali Reza
authors.initials: AR
authors.lastname: Nazmi
authors.affiliation: Maurice Wilkins Centre, Biomolecular Interaction Centre, Christchurch, 8140, New Zealand.|Department of Chemistry, University of Canterbury, Christchurch, 8140, New Zealand.
authors.forename: Emily J
authors.initials: EJ
authors.lastname: Parker
mesh_terms: D001276:ATP Phosphoribosyltransferase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000737:chemistry*; D000255:Adenosine Triphosphate / Q000737:chemistry*; D000494:Allosteric Regulation; D000495:Allosteric Site; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001667:Binding, Competitive; D016123:Campylobacter jejuni / Q000737:chemistry* / Q000201:enzymology / Q000235:genetics; D003001:Cloning, Molecular; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006639:Histidine / Q000737:chemistry*; D007700:Kinetics; D008958:Models, Molecular; D009154:Mutation; D017510:Protein Folding; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D001426:Bacterial Proteins; D011994:Recombinant Proteins; D000249:Adenosine Monophosphate; D006639:Histidine; D000255:Adenosine Triphosphate; D001276:ATP Phosphoribosyltransferase
keywords: ATP-PRT; HisG; allostery; conformational change; phosphoribosyltransferase