A dimeric catalytic core relates the short and long forms of ATP-phosphoribosyltransferase

Biochem J. 2018 Jan 5;475(1):247-260. doi: 10.1042/BCJ20170762.


Adenosine triphosphate (ATP) phosphoribosyltransferase (ATP-PRT) catalyses the first committed step of histidine biosynthesis in plants and microorganisms. Two forms of ATP-PRT have been reported, which differ in their molecular architecture and mechanism of allosteric regulation. The short-form ATP-PRT is a hetero-octamer, with four HisG chains that comprise only the catalytic domains and four separate chains of HisZ required for allosteric regulation by histidine. The long-form ATP-PRT is homo-hexameric, with each chain comprising two catalytic domains and a covalently linked regulatory domain that binds histidine as an allosteric inhibitor. Here, we describe a truncated long-form ATP-PRT from Campylobacter jejuni devoid of its regulatory domain (CjeATP-PRTcore). Results showed that CjeATP-PRTcore is dimeric, exhibits attenuated catalytic activity, and is insensitive to histidine, indicating that the covalently linked regulatory domain plays a role in both catalysis and regulation. Crystal structures were obtained for CjeATP-PRTcore in complex with both substrates, and for the first time, the complete product of the reaction. These structures reveal the key features of the active site and provide insights into how substrates move into position during catalysis.

Keywords: allosteric regulation; phosphoribosyltransferase; protein structure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Phosphoribosyltransferase / chemistry*
  • ATP Phosphoribosyltransferase / genetics
  • ATP Phosphoribosyltransferase / metabolism
  • Adenosine Monophosphate / chemistry*
  • Adenosine Monophosphate / metabolism
  • Adenosine Triphosphate / chemistry*
  • Adenosine Triphosphate / metabolism
  • Allosteric Regulation
  • Amino Acid Motifs
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Campylobacter jejuni / chemistry
  • Campylobacter jejuni / enzymology*
  • Catalytic Domain
  • Cloning, Molecular
  • Crystallography, X-Ray
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Gene Expression
  • Genetic Vectors / chemistry
  • Genetic Vectors / metabolism
  • Histidine / chemistry
  • Histidine / metabolism
  • Isoenzymes / chemistry
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Kinetics
  • Models, Molecular
  • Protein Binding
  • Protein Conformation, alpha-Helical
  • Protein Conformation, beta-Strand
  • Protein Interaction Domains and Motifs
  • Protein Multimerization
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Substrate Specificity


  • Bacterial Proteins
  • Isoenzymes
  • Recombinant Proteins
  • Adenosine Monophosphate
  • Histidine
  • Adenosine Triphosphate
  • ATP Phosphoribosyltransferase