The structure of Staphylococcus aureus phosphopantetheine adenylyltransferase in complex with 3'-phosphoadenosine 5'-phosphosulfate reveals a new ligand-binding mode

Acta Crystallogr Sect F Struct Biol Cryst Commun. 2009 Oct 1;65(Pt 10):987-91. doi: 10.1107/S1744309109036616. Epub 2009 Sep 23.


Bacterial phosphopantetheine adenylyltransferase (PPAT) catalyzes the penultimate step in the coenzyme A (CoA) biosynthetic pathway. It catalyzes the reversible transfer of an adenylyl group from ATP to 4'-phosphopantetheine (Ppant) to form dephospho-CoA (dPCoA) and pyrophosphate. Previous structural studies have revealed how several ligands are recognized by bacterial PPATs. ATP, ADP, Ppant and dPCoA bind to the same binding site in a highly similar manner, while CoA binds to a partially overlapping site in a different mode. To provide further structural insights into ligand binding, the crystal structure of Staphylococcus aureus PPAT was solved in a binary complex with 3'-phosphoadenosine 5'-phosphosulfate (PAPS). This study unexpectedly revealed a new mode of ligand binding to PPAT, thus providing potentially useful information for structure-based discovery of inhibitors of bacterial PPATs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Crystallography, X-Ray
  • Models, Molecular
  • Molecular Sequence Data
  • Nucleotidyltransferases / chemistry*
  • Nucleotidyltransferases / metabolism
  • Phosphoadenosine Phosphosulfate / metabolism*
  • Protein Structure, Quaternary
  • Sequence Alignment
  • Staphylococcus aureus / enzymology


  • Phosphoadenosine Phosphosulfate
  • Nucleotidyltransferases
  • pantetheine-phosphate adenylyltransferase